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The present disclosure provides processes for the N-dealkylation of tertiary amines and the use of transition metal catalysts to prepare tertiary N-allyl amine derivatives and secondary amine derivatives thereof. The tertiary amines can be alkaloids and, more particularly, the tertiary amines can be

The present disclosure provides processes for the N-dealkylation of tertiary amines and the use of transition metal catalysts to prepare tertiary N-allyl amine derivatives and secondary amine derivatives thereof. The tertiary amines can be alkaloids and, more particularly, the tertiary amines can be opioids. In specific embodiments, the present disclosure provides methods for use in processes for the synthesis of naloxone and naltrexone from oripavine.

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1. A method for making a compound of Formula (41): comprising: (a) contacting a compound of Formula (45): with a compound of Formula (10): to provide a compound of Formula (60): (b) contacting the compound of Formula (60) with an alkoxide of Formula (61): to provide the compound of Formula (95):

1. A method for making a compound of Formula (41): comprising: (a) contacting a compound of Formula (45): with a compound of Formula (10): to provide a compound of Formula (60): (b) contacting the compound of Formula (60) with an alkoxide of Formula (61): to provide the compound of Formula (95): and (c) contacting the compound of Formula (95) with a transition metal catalyst to provide the compound of Formula (41), wherein: X is selected from —Cl, —Br, and —I;R9 is selected from phenyl and 4-nitro-phenyl;R14 and R16 are each independently selected from —OH, —H, and —OR17;R15 is selected from —OH, —H, —OR17, ═O, and ═CH2;R17 is an oxygen protecting group;R14′ and R16′ are each independently selected from —OH, —H, —OR17, and —OC(O)OR9;R15′ is selected from —OH, —H, —OR17,═O, ═CH2, and —OC(O)OR9;andM is selected from the group consisting of Na, K, and Li. 2. The method of claim 1, wherein R14 and R16 are each independently selected from —H and —OR17 and R15 is selected from —H, —OR17, ═O, and ═CH2. 3. The method of claim 1, wherein: the oxygen protecting group is selected from the group consisting of allyl, benzoyl, benzyl, β-methoxyethoxymethyl, dimethoxytrityl, methoxymethyl, para-methoxybenzyl, methylthiomethyl, pivaloyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldimethylsilyloxymethyl, tri-iso-propylsilyl, methyl, ethoxyethyl, —C(O)O—CH2—CH═CH2, tert-butyl-diphenylsilyl, [bis-(4-methoxyphenyl)phenylmethyl)], triphenylmethyl, —C(O)(C1-C4) alkyl, —C(O)OR18, and —(C1-C6) alkyl, each alkyl being unsubstituted or substituted with 1, 2, 3, 4, or 5 independently-selected R21 groups;each R18 is independently selected from —(C1-C6) alkyl, —(C2-C6) alkenyl, and —(C2-C6) alkynyl, each alkyl, alkenyl, and alkynyl being unsubstituted or substituted with 1, 2, 3, 4, or 5 independently-selected R21 groups; andeach R21 is independently selected from —Cl, —Br, —I, —NH2, —CN, and phenyl. 4. The method of claim 3, wherein the oxygen protecting group is allyl, benzoyl, benzyl, β-methoxyethoxymethyl, dimethoxytrityl, methoxymethyl, para-methoxybenzyl, methylthiomethyl, pivaloyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldimethylsilyloxymethyl, tri-iso-propylsilyl, methyl, ethoxyethyl, or —C(O)O—CH2—CH═CH2. 5. The method of claim 2, wherein: the oxygen protecting group is selected from the group consisting of allyl, benzoyl, benzyl, β-methoxyethoxymethyl, dimethoxytrityl, methoxymethyl, para-methoxybenzyl, methylthiomethyl, pivaloyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldimethylsilyloxymethyl, tri-iso-propylsilyl, methyl, ethoxyethyl, —C(O)O—CH2—CH═CH2, tert-butyl-diphenylsilyl, [bis-(4-methoxyphenyl)phenylmethyl)], triphenylmethyl, —C(O)(C1-C4) alkyl, —C(O)OR18, and —(C1-C6) alkyl, each alkyl being unsubstituted or substituted with 1, 2, 3, 4, or 5 independently-selected R21 groups;each R18 is independently selected from —(C1-C6) alkyl, —(C2-C6) alkenyl, and —(C2-C6) alkynyl, each alkyl, alkenyl, and alkynyl being unsubstituted or substituted with 1, 2, 3, 4, or 5 independently-selected R21 groups; andeach R21 is independently selected from —Cl, —Br, —I, —NH2, —CN, and phenyl. 6. The method of claim 5, wherein the oxygen protecting group is allyl, benzoyl, benzyl,β-methoxyethoxymethyl, dimethoxytrityl, methoxymethyl, para-methoxybenzyl, methylthiomethyl, pivaloyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldimethylsilyloxymethyl, tri-iso-propylsilyl, methyl, ethoxyethyl, or —C(O)O—CH2—CH═CH2. 7. The method of claim 1, wherein the contacting in step (a) occurs in a solvent, wherein the solvent is selected from the group consisting of chloroform, dichloromethane, 1,2-dichloroethane, toluene, tetrahydrofuran, ethyl acetate, acetone, tert-amyl alcohol, tert-butyl alcohol, 3-methyl-3-pentanol, 2,3-dimethyl-3-pentanol, 3-ethyl-pentanol, 2-methyl-2-hexanol, acetonitrile, benzene, carbon tetrachloride, chlorobenzene, 1,2-dichlorobenzene, N,N-dimethylformamide, trifluorotoluene, 1,4-dioxane, 1,2-dimethoxyethane, xylene, and combinations of two or more thereof. 8. The method of claim 7, wherein the solvent comprises tert-amyl alcohol, dichloromethane, tetrahydrofuran, or combinations of two or more thereof. 9. The method of claim 1, wherein the contacting in step (b) occurs in a solvent, wherein the solvent is selected from the group consisting of chloroform, dichloromethane, 1,2-dichloroethane, toluene, tetrahydrofuran, ethyl acetate, acetone, tert-amyl alcohol, tert-butyl alcohol, 3-methyl-3-pentanol, 2,3-dimethyl-3-pentanol, 3-ethyl-pentanol, 2-methyl-2-hexanol, acetonitrile, benzene, carbon tetrachloride, chlorobenzene, 1,2-dichlorobenzene, N,N-dimethylformamide, trifluorotoluene, 1,4-dioxane, 1,2-dimethoxyethane, xylene, and combinations of two or more thereof. 10. The method of claim 9, wherein the solvent comprises tert-amyl alcohol, dichloromethane, tetrahydrofuran, or combinations of two or more thereof. 11. The method of claim 1, wherein the transition metal catalyst comprises a transition metal selected from the group consisting of Pd[0], Pd[II], Ni[0], Ni[II], Mo[0], Ru[II], Rh[I], and combinations of two or more thereof. 12. The method of claim 11, wherein the transition metal catalyst is selected from the group consisting of Pd(PPh3)4, Pd(Ph2P(CH2)4PPh2)2, Ni(PPh3)4, Ni(Ph2P(CH2)4PPh2)2, ((pentamethylcyclopentadienyl)RuCl)4, [Pd(DBA)2]/PPh3, [Pd(OAc)2]/PPh3, [Ni(COD)2]/PPh3, NiCl2/PPh3, Ni[P(OEt)3]4, [Mo(CO)6-DPPE], RhH(PPh3)4—P(n-Bu)3, and combinations of two or more thereof. 13. The method of claim 2, wherein the transition metal catalyst comprises a transition metal selected from the group consisting of Pd[0], Pd[II], Ni[0], Ni[II], Ru[II], and combinations of two or more thereof. 14. The method of claim 13, wherein the transition metal catalyst is selected from the group consisting of Pd(PPh3)4, Pd(Ph2P(CH2)4PPh2)2, Ni(PPh3)4, Ni(Ph2P(CH2)4PPh2)2, ((pentamethylcyclopentadienyl)RuCl)4, [Pd(DBA)2]/PPh3, [Pd(OAc)2]/PPh3, [Ni(COD)2]/PPh3, NiCl2/PPh3, Ni[P(OEt)3]4, and combinations of two or more thereof. 15. The method of claim 4, wherein the transition metal catalyst comprises a transition metal selected from the group consisting of Pd[0], Pd[II], Ni[0], Ni[II], Ru[II], and combinations of two or more thereof. 16. The method of claim 15, wherein the transition metal catalyst is selected from the group consisting of Pd(PPh3)4, Pd(Ph2P(CH2)4PPh2)2, Ni(PPh3)4, Ni(Ph2P(CH2)4PPh2)2, ((pentamethylcyclopentadienyl)RuCl)4, [Pd(DBA)2]/PPh3, [Pd(OAc)2]/PPh3, [Ni(COD)2]/PPh3, NiCl2/PPh3, Ni[P(OEt)3]4, and combinations of two or more thereof. 17. The method of claim 6, wherein the transition metal catalyst comprises a transition metal selected from the group consisting of Pd[0], Pd[II], Ni[0], Ni[II], Ru[II], and combinations of two or more thereof. 18. The method of claim 17, wherein the transition metal catalyst is selected from the group consisting of Pd(PPh3)4, Pd(Ph2P(CH2)4PPh2)2, Ni(PPh3)4, Ni(Ph2P(CH2)4PPh2)2, ((pentamethylcyclopentadienyl)RuCl)4, [Pd(DBA)2]/PPh3, [Pd(OAc)2]/PPh3, [Ni(COD)2]/PPh3, NiCl2/PPh3, Ni[P(OEt)3]4, and combinations of two or more thereof. 19. The method of claim 1, wherein the contacting in step (c) occurs in a solvent, wherein the solvent is selected from the group consisting of chloroform, dichloromethane, 1,2-dichloroethane, toluene, tetrahydrofuran, ethyl acetate, acetone, tert-amyl alcohol, tert-butyl alcohol, 3-methyl-3-pentanol, 2,3-dimethyl-3-pentanol, 3-ethyl-pentanol, 2-methyl-2-hexanol, acetonitrile, benzene, carbon tetrachloride, chlorobenzene, 1,2-dichlorobenzene, N,N-dimethylformamide, trifluorotoluene, 1,4-dioxane, 1,2-dimethoxyethane, xylene, and combinations of two or more thereof. 20. The method of claim 19, wherein the solvent comprises tert-amyl alcohol, dichloromethane, tetrahydrofuran, or combinations of two or more thereof. 21. The method of claim 19, wherein the transition metal catalyst comprises a transition metal selected from the group consisting of Pd[0], Pd[II], Ni[0], Ni[II], Ru[II], and combinations of two or more thereof. 22. The method of claim 21, wherein the transition metal catalyst is selected from the group consisting of Pd(PPh3)4, Pd(Ph2P(CH2)4PPh2)2, Ni(PPh3)4, Ni(Ph2P(CH2)4PPh2)2, ((pentamethylcyclopentadienyl)RuCl)4, [Pd(DBA)2]/PPh3, [Pd(OAc)2]/PPh3, [Ni(COD)2]/PPh3, NiCl2/PPh3, Ni[P(OEt)3]4, and combinations of two or more thereof. 23. The method of claim 2, wherein the contacting in step (a) occurs in a solvent, wherein the solvent is selected from the group consisting of chloroform, dichloromethane, 1,2-dichloroethane, toluene, tetrahydrofuran, ethyl acetate, acetone, tert-amyl alcohol, tert-butyl alcohol, 3-methyl-3-pentanol, 2,3-dimethyl-3-pentanol, 3-ethyl-pentanol, 2-methyl-2-hexanol, acetonitrile, benzene, carbon tetrachloride, chlorobenzene, 1,2-dichlorobenzene, N,N-dimethylformamide, trifluorotoluene, 1,4-dioxane, 1,2-dimethoxyethane, xylene, and combinations of two or more thereof. 24. The method of claim 23, wherein the solvent comprises tert-amyl alcohol, dichloromethane, tetrahydrofuran, or combinations of two or more thereof. 25. The method of claim 2, wherein the contacting in step (b) occurs in a solvent, wherein the solvent is selected from the group consisting of chloroform, dichloromethane, 1,2-dichloroethane, toluene, tetrahydrofuran, ethyl acetate, acetone, tert-amyl alcohol, tert-butyl alcohol, 3-methyl-3-pentanol, 2,3-dimethyl-3-pentanol, 3-ethyl-pentanol, 2-methyl-2-hexanol, acetonitrile, benzene, carbon tetrachloride, chlorobenzene, 1,2-dichlorobenzene, N,N-dimethylformamide, trifluorotoluene, 1,4-dioxane, 1,2-dimethoxyethane, xylene, and combinations of two or more thereof. 26. The method of claim 25, wherein the solvent comprises tert-amyl alcohol, dichloromethane, tetrahydrofuran, or combinations of two or more thereof. 27. The method of claim 2, wherein the contacting in step (c) occurs in a solvent, wherein the solvent is selected from the group consisting of chloroform, dichloromethane, 1,2-dichloroethane, toluene, tetrahydrofuran, ethyl acetate, acetone, tert-amyl alcohol, tert-butyl alcohol, 3-methyl-3-pentanol, 2,3-dimethyl-3-pentanol, 3-ethyl-pentanol, 2-methyl-2-hexanol, acetonitrile, benzene, carbon tetrachloride, chlorobenzene, 1,2-dichlorobenzene, N,N-dimethylformamide, trifluorotoluene, 1,4-dioxane, 1,2-dimethoxyethane, xylene, and combinations of two or more thereof. 28. The method of claim 27, wherein the solvent comprises tert-amyl alcohol, dichloromethane, tetrahydrofuran, or combinations of two or more thereof. 29. The method of claim 1, wherein R15′ is selected from —OH, —H, —OR17, ═CH2, and —OC(O)OR9.