IP Library › Granted Patent US 7,323,565
Granted Patent B2
US 7,323,565 · App. 10/495,503 · Granted Jan 29, 2008

Method for the catalytic production of hydrocodone and hydromorphone

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Quick Facts
Patent No.
US 7,323,565
App. No.
10/495,503
Granted
Jan 29, 2008
Kind
B2
Abstract

A method for the catalytic conversion of codeine, morphine or analogs thereof into hydrocodone, hydromorphone or analogs thereof utilizing a transition metal complex of a tertiary phosphine halide as catalyst.

Claims (19)

1. A method comprising catalytically converting a compound of Formula I into a compound of Formula II utilizing at least one transition metal complex of a tertiary phosphine halide, wherein R 1 is H, alkyl, aryl or acyl and

wherein the metal complex is of the formula [M(PR 2 3 ) n X m ] p wherein M is a Group VIII transition metal, R 2 is an alkyl or aryl, X is H, a halide or halide compound, n is 1, 2, 3 or 4, p is at least 1 and m is 1 or 2

2. The method according to claim 1 wherein R 1 is H or CH 3 .

3. The method of claim 1 wherein the metal complex is of the formula [Rh(PR 2 3 ) n X] p , wherein R 2 is an alkyl or aryl, X is a halide or halide compound, n is 1, 2 or 3 and p is at least 1.

4. The method of claim 1 wherein the metal complex having the formula [Rh(PR 2 3 ) n Y] p , wherein n is 1, 2 or 3, p is at least 1 and Y is selected from the group consisting of BF 4 , PF 6 , ClO 4 and OCOCF 3 .

5. The method of claim 1 wherein in the metal complex is of the formula [RuX 2 (PR 2 3 ) n ] p wherein R 2 is an alkyl or aryl, X is a halide, n is 1, 2, 3 or 4 and p is at least 1.

6. The method of claim 1 wherein the metal complex is of the formula [RuYX(PR 2 3 ) n ] p wherein R 2 is an alkyl or aryl and wherein n=3, p is at least 1, Y═H and X═Cl; or n=3, p is at least 1, Y═H and X═H; or n=4, p is at least 1, X═H, Y═H; or n=2, 3 or 4 and X═Y is selected from the group consisting of ClO 4 , CF 3 SO 3 , PF 6 and BF 4 .

7. A method for producing hydrocodone comprising converting codeine into hydrocodone in the presence of at least one transition metal complex of a tertiary phosphine halide wherein the metal complex is of the formula [M(PR 2 3 ) n X m ] p wherein M is a Group VIII-transition metal, R 2 is an alkyl or aryl, X is H, a halide or halide compound, n is 1, 2, 3 or 4, p is at least 1 and m is 1 or 2.

8. The method of claim 7 wherein the metal complex is of the formula [Rh(PR 2 3 ) n X] p , wherein R 2 is an alkyl or aryl, X is a halide or halide compound, n is 1, 2 or 3 and p is at least 1.

9. The method of claim 7 wherein the metal complex is of the formula [Rh(PR 2 3 ) n Y] p , wherein R 2 is an alkyl or aryl, n is 1, 2 or 3, p is at least 1 and Y is selected from the group consisting of BF 4 , PF 6 , ClO 4 and OCOCF 3 .

10. The method of claim 7 wherein in the metal complex is of the formula [RuX 2 (PR 2 3 ) n ] p wherein R 2 is an alkyl or aryl, X is a halide, n is 1, 2, 3 or 4 and p is at least 1.

11. The method of claim 7 wherein the metal complex is of the formula [RuYX(PR 2 3 ) n ] p wherein R 2 is an alkyl or aryl and wherein n=3, p is at least 1, Y═H and X═Cl; or n=3, p is at least 1, Y═H and X═H; or n=4, X═H, Y═H; or n=2, 3 or 4, p is at least 1 and X═Y is selected from the group consisting of ClO 4 , CF 3 SO 3 , PF 6 and BF 4 .

12. A method for producing hydrocodone comprising converting codeine into hydrocodone in the presence of at least one catalyst, wherein the catalyst includes RhCl(P(C 6 H 5 ) 3 ) 3 or [Ru(P(C 6 H 5 ) 3 ) 2 Cl 2 ] 2 .

13. A method for producing hydromorphone comprising converting morphine into hydromorphone in the presence of at least one transition metal complex of a tertiary phosphine halide_wherein the metal complex is of the formula [M(PR 2 3 ) n X m ] p wherein M is a Group VIII -transition metal, R 2 is an alkyl or aryl, X is a halide or halide compound, n is 1, 2, 3 or 4, p is at least 1 and m is 1 or 2.

14. The method of claim 13 wherein the metal complex is of the formula [Rh(PR 2 3 ) n X] p , wherein R 2 is an alkyl or aryl, X is a halide or halide compound, n is 1, 2 or 3 and p is at least 1.

15. The method of claim 13 wherein the metal complex is of the formula [Rh(PR 2 3 ) n Y] p , wherein R 2 is an alkyl or aryl, n is 1, 2 or 3, p is at least 1 and Y is selected from the group consisting of BF 4 , PF 6 , ClO 4 and OCOCF 3 .

16. The method of claim 13 wherein in the metal complex is of the formula [RuX 2 (PR 2 3 ) n ] p wherein R 2 is an alkyl or aryl, X is a halide, n is 1, 2, 3 or 4 and p is at least 1.

17. The method of claim 13 wherein the metal complex is of the formula [RuYX(PR 2 3 ) n ] p wherein R 2 is an alkyl or aryl and wherein n=3, Y═H and X═Cl; or n=3, Y═H, p is at least 1 and X═H; or n=4, p is at least 1, X═H, Y═H; or n=2, 3 or 4, p is at least 1 and X═Y is selected from the group consisting of ClO 4 , CF 3 SO 3 H, PF 6 and BF 4 .

18. A method for producing hydromorphone comprising converting morphine into hydromorphone in the presence of at least one catalyst, wherein the catalyst includes RhCl(P(C 6 H 5 ) 3 ) 3 or [Ru(P(C 6 H 5 ) 3 ) 2 Cl 2 ] 2 .

Assignments (3)
RELEASE OF PATENT SECURITY INTERESTS RECORDED AT REEL 032480, FRAME 0001 Recorded Nov 16, 2023
From: DEUTSCHE BANK AG NEW YORK BRANCH, AS COLLATERAL AGENT
To: THERAKOS, INC.; MALLINCKRODT INTERNATIONAL FINANCE S.A.; MALLINCKRODT CB LLC; MALLINCKRODT FINANCE GMBH; MALLINCKRODT US HOLDINGS LLC (F/K/A MALLINCKRODT US HOLDINGS INC.); MALLINCKRODT CARRIBEAN, INC.; MALLINCKRODT US POOL LLC; MNK 2011 LLC (F/K/A MALLINCKRODT INC.); LUDLOW LLC (F/K/A LUDLOW CORPORATION); CNS THERAPEUTICS, INC.; MALLINCKRODT ENTERPRISES HOLDINGS LLC (F/K/A MALLINCKRODT ENTERPRISES HOLDINGS, INC.); MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; LAFAYETTE PHARMACEUTICALS LLC; LIEBEL-FLARSHEIM COMPANY LLC; MALLINCKRODT BRAND PHARMACEUTICALS LLC (F/K/A MALLINCKRODT BRAND PHARMACEUTICALS, INC.); MALLINCKRODT VETERINARY, INC.; MALLINCKRODT US HOLDINGS LLC; IMC EXPLORATION COMPANY; MEH, INC.; MALLINCKRODT HOSPITAL PRODUCTS IP UNLIMITED COMPANY (F/K/A MALLINCKRODT HOSPITAL PRODUCTS IP LIMITED); MALLINCKRODT ARD IP UNLIMITED COMPANY (F/K/A MALLINCKRODT ARD IP LIMITED); OCERA THERAPEUTICS LLC (F/K/A OCERA THERAPEUTICS, INC.); SPECGX LLC; STRATATECH CORPORATION; SUCAMPO PHARMA AMERICAS LLC; VTESSE LLC (F/K/A VTESSE INC.); MALLINCKRODT PHARMACEUTICALS IRELAND LIMITED; MALLINCKRODT PHARMA IP TRADING UNLIMITED COMPANY (F/K/A MALLINCKRODT PHARMA IP TRADING D.A.C.); INFACARE PHARMACEUTICAL CORPORATION; ST SHARED SERVICES LLC; IKARIA THERAPEUTICS LLC; INO THERAPEUTICS LLC
Reel/Frame 065609/0322 →
SECURITY INTEREST Recorded Mar 19, 2014
From: MALLINCKRODT INTERNATIONAL FINANCE S.A.; MALLINCKRODT CB LLC; MALLINCKRODT FINANCE GMBH; MALLINCKRODT US HOLDINGS INC.; MALLINCKRODT CARIBBEAN, INC.; MALLINCKRODT US POOL LLC; MALLINCKRODT INC.; LUDLOW CORPORATION; CNS THERAPEUTICS, INC.; ENTERPRISES HOLDINGS, INC.; MALLINCKRODT ENTERPRISES LLC; MALLINCKRODT LLC; LAFAYETTE PHARMACEUTICALS LLC; LIEBEL-FLARSHEIM COMPANY LLC; MALLINCKRODT BRAND PHARMACEUTICALS, INC; MALLINCKRODT VETERINARY, INC.; MALLINCKRODT US HOLDINGS LLC; IMC EXPLORATION COMPANY; MEH, INC; MALLINCKRODT ENTERPRISES HOLDINGS, INC.
To: DEUTSCHE BANK AG NEW YORK BRANCH
Reel/Frame 032480/0001 →
CHANGE OF LEGAL ENTITY Recorded Aug 16, 2011
From: MALLINCKRODT INC.
To: MALLINCKRODT LLC
Reel/Frame 026754/0001 →