Process for the preparation of an indole derivative

• US 6,946,565 B2
• Filed: 01/30/2003
• Issued: 09/20/2005
• Est. Priority Date: 07/16/1998
• Status: Expired due to Fees

• Current Assignee: Smithkline Beecham PLC (GSK plc)
• Original Assignee: Smithkline Beecham PLC (GSK plc)
• Inventors: Strachan, John Bryce, Fedouloff, Michael
• Primary Examiner(s): Rotman, Alan L.
• Assistant Examiner(s): Robinson, Binta
• Application Number:
  US10/354,865
• Publication Number:
  US 20030114684A1
• Time in Patent Office: 964 Days
• Field of Search: 548/492
• US Class Current: 549/492
• CPC Class Codes: C07D 209/42 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

A process for the preparation of methyl 2-(3-chloropropoxy)-indole-3-carboxylate, which comprises reacting a 3-chloro-3-carboxylate indole compound with 3-chloropropanol in the presence of an acid having a pKa of from 0 to 2.

Claims

1. A process for the preparation of methyl 2-(3-chloropropoxy)-indole-3-carboxylate, namely the compound of formula (B):

which process comprises reacting a compound of formula (C)

with 3-chloropropanol in the presence of an acid having a pKa of from 0 to 2, wherein the acid is trichloroacetic acid, dichloroacetic acid and/or trifluoroacetic acid.

2. A process as claimed in claim 1 in which the reaction is effected in an organic solvent.

3. A process as claimed in claim 2 in which the organic solvent is dichloromethane or chloroform.

4. A process as claimed in claim 3 wherein the reaction is effected using a catalytic amount of the acid.

5. A process for the preparation of methyl 2-(3-chloropropoxy)-indole-3-carboxylate, namely the compound of formula (B):

which process comprises reacting a compound of formula (C)

with 3-chloropropanol in the presence of an acid having a pKa of from 0 to 2, wherein the reaction is effected in an organic solvent at a temperature in the range −

20°

C. to +10°

C.

6. A process as claimed in claim 5 in which the acid is trichloroacetic acid, dichloroacetic acid and/or trifluoroacetic acid.

7. A process as claimed in claim 5 in which the acid is trichloroacetic acid.

8. A process as claimed in claim 5 in which the organic solvent is dichloromethane or chloroform.

9. A process as claimed in claim 6 in which the organic solvent is dichloromethane or chloroform.

10. A process as claimed in claim 5 wherein the reaction is effected using a catalytic amount of the acid.

11. A process as claimed in claim 9 wherein the reaction is effected using a catalytic amount of the acid.