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Details for Patent: 5,512,701

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Details for Patent: 5,512,701

Title: Process for the synthesis of vinyl sulfenic acid derivatives
Abstract:The present invention is directed to a new process for the synthesis of vinyl sulfenic acid derivatives. These compounds are useful for the synthesis of benzo[b]thiophenes, in particular 2-aryl-benzo[b]thiophenes.
Inventor(s): Hoard; David W. (Lafayette, IN), Luke; Wayne D. (West Lafayette, IN)
Assignee: Eli Lilly and Company (Indianapolis, IN)
Filing Date:Jun 07, 1995
Application Number:08/482,692
Claims:1. A process for preparing a compound of the formula ##STR22## wherein: R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, or amino;

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, or amino;

R.sub.4 is OSi(R).sub.3, NR.sub.5 R.sub.6, or SR.sub.8 ;

each R is independently C.sub.1 -C.sub.6 alkyl, aryl, or arylalkyl;

R.sub.5 and R.sub.6 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, arylalkyl, or aryl; or R.sub.5 and R.sub.6 together with the nitrogen atom form a ring selected from piperidine, pyrrolidine, morpholine, or hexamethylimine; and

R.sub.8 is C.sub.1 -C.sub.6 alkyl, aryl, or arylalkyl;

which comprises:

(1) reacting a compound of the formula ##STR23## wherein: R.sub.1 and R.sub.2 are as defined above, and

R.sub.3 is a thermally-labile or acid-labile C.sub.2 -C.sub.10 alkyl, C.sub.4 -C.sub.10 alkenyl, or aryl(C.sub.1 -C.sub.10 alkyl) group; with a silylating reagent to produce a sulfenate silyl ester of the formula ##STR24## wherein: R.sub.1 and R.sub.2 are as defined above;

R.sub.7 is OSi(R).sub.3 ; and

each R is independently C.sub.1 -C.sub.6 alkyl, aryl, or arylalkyl;

(2) optionally reacting said sulfenate silyl ester with an amine of the formula HNR.sub.5 R.sub.6 wherein R.sub.5 and R.sub.6 are as defined above; or

(3) optionally reacting said sulfenate silyl ester with a mercaptan of the formula HSR.sub.8, wherein R.sub.8 is as defined above, in the presence of an amine base.

2. The process of claim 1 for preparing a compound of the formula ##STR25## wherein: R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, or amino;

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, or amino;

R.sub.7 is OSi(R).sub.3 ; and

each R is independently C.sub.1 -C.sub.6 alkyl, aryl, or arylalkyl; which comprises reacting a compound of the formula ##STR26## wherein: R.sub.1 and R.sub.2 are as defined above, and

R.sub.3 is a thermally-labile or acid-labile C.sub.2 -C.sub.10 alkyl, C.sub.4 -C.sub.10 alkenyl, or aryl(C.sub.1 -C.sub.10 alkyl) group; with a silylating reagent.

3. The process of claim 2 wherein:

R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy; and

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy.

4. The process of claim 3 wherein:

R.sub.7 is OTMS, OTES, OTIPS, ODMIPS, ODEIPS, OTDS, OTBDMS, OTBDPS, OTBS, OTPS, ODPMS, or OTBMPS.

5. The process of claim 4 wherein the silylating reagent is a bis(trialkylsilyl)urea or a combination of a hexaalkyldisilylzane and a catalytic amount of a chlorotrialkylsilane, and R is C.sub.1 -C.sub.6 alkyl.

6. The process of claim 5 wherein the silylating reagent is bis(trimethylsilyl)urea and R is methyl.

7. The process of claim 6 wherein R.sub.3 is a thermally-labile or acid-labile C.sub.2 -C.sub.10 alkyl group.

8. The process of claim 7 wherein R.sub.1 and R.sub.2 are methoxy, and R.sub.3 is t-butyl.

9. The process of claim 1 for preparing a compound of the formula ##STR27## wherein: R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, amino;

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, amino; and

R.sub.5 and R.sub.6 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, or aryl, or R.sub.5 and R.sub.6 together with the nitrogen atom form a ring selected from piperidine, pyrrolidine, morpholine, or hexamethylimine;

comprising the steps of:

(1) reacting a compound of the formula ##STR28## wherein: R.sub.1 and R.sub.2 are as defined above, and

R.sub.3 is a thermally-labile or acid-labile C.sub.2 -C.sub.10 alkyl, C.sub.4 -C.sub.10 alkenyl, or aryl(C.sub.1 -C.sub.10 alkyl) group; with a silylating reagent to produce a sulfenate silyl ester of the formula ##STR29## wherein: R.sub.1 and R.sub.2 are as defined above;

R.sub.7 is OSi(R).sub.3 ; and

each R is independently C.sub.1 -C.sub.6 alkyl, aryl, or arylalkyl; and

(2) reacting said sulfenate silyl ester with an amine of the formula HNR.sub.5 R.sub.6 wherein R.sub.5 and R.sub.6 are as defined above.

10. The process of claim 9 wherein:

R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy; and

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy.

11. The process of claim 10 wherein the silylating reagent is bis(trimethylsilyl)urea and R is methyl.

12. The process of claim 11 wherein R.sub.3 is a thermally-labile or acid-labile C.sub.2 -C.sub.10 alkyl group.

13. The process of claim 12 wherein R.sub.1 and R.sub.2 are methoxy, and R.sub.3 is t-butyl.

14. The process of claim 13 wherein R.sub.5 and R.sub.6 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, or aryl.

15. The process of claim 14 wherein R.sub.5 and R.sub.6 are methyl, or R.sub.5 is hydrogen and R.sub.6 is benzyl.

16. The process of claim 1 for preparing a compound of the formula ##STR30## wherein: R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, amino;

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, amino; and

R.sub.8 is C.sub.1 -C.sub.6 alkyl, aryl, or arylalkyl

comprising the steps of:

(1) reacting a compound of the formula ##STR31## wherein: R.sub.1 and R.sub.2 are as defined above, and

R.sub.3 is a thermally-labile or acid-labile C.sub.2 -C.sub.10 alkyl, C.sub.4 -C.sub.10 alkenyl, or aryl(C.sub.1 -C.sub.10 alkyl) group; with a silylating reagent to produce a sulfenate silyl ester of the formula ##STR32## wherein: R.sub.1 and R.sub.2 are as defined above;

R.sub.7 is OSi(R).sub.3 ; and

each R is independently C.sub.1 -C.sub.6 alkyl, aryl, or arylalkyl; and

(2) reacting said sulfenate silyl ester with a mercaptan of the formula HSR.sub.8, where R.sub.8 is as defined above, in the presence of an amine base.

17. The process of claim 16 wherein:

R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy; and

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy.

18. The process of claim 17 wherein the amine base is triethylamine, diisopropylethylamine, or pyridine.

19. The process of claim 18 wherein the silylating reagent is bis(trimethylsilyl)urea and R is methyl.

20. The process of claim 19 wherein R.sub.3 is a thermally-labile or acid-labile C.sub.2 -C.sub.10 alkyl group.

21. The process of claim 20 wherein the amine base is triethylamine.

22. The process of claim 21 wherein R.sub.1 and R.sub.2 are methoxy and R.sub.3 is t-butyl.

23. The process of claim 22 wherein R.sub.8 is C.sub.1 -C.sub.6 alkyl.

24. The process of claim 23 wherein R.sub.8 is ethyl.
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