Browse Prior Art Database

Suzuki coupling

IP.com Disclosure Number: IPCOM000198368D
Publication Date: 2010-Aug-05
Document File: 3 page(s) / 29K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 51% of the total text.

Page 1 of 3

SUZUKI COUPLING

The Suzuki reaction is the organic reaction of an aryl- or vinyl-boronic acid with an aryl- or vinyl-halide catalyzed by a palladium(0) complex. It is widely used to synthesize poly- olefins, styrenes, and substituted biphenyls, and has been extended to incorporate alkyl bromides.

In pharmaceuticals, there is very wide scope of Suzuki coupling, for example, sartans derivative possessing an aryl group have attracted considerable interest due to their utility in the development of compounds of potential pharmacological interest.

Provided are processes for the preparation of Sartans intermediates via Suzuki coupling:

Example 1: Preparation of 2-n-butyl-3-{[2'-(1-trityl-1H-tetrazol-5-yl) biphen-4-yl] methyl} -1, 3-diazaspiro [4, 4] non-1-ene- 4-one.

Pd(OAC)2 was added to a mixture of triphenyl phosphine in toluene at room temperature, then. Na2SO3 was added and the reaction was stirred. 2-(1H-tetrazol-5-yl)phenylboronic acid was added. Distilled water, 2-butyl-3(4'-bromobenzyl)-1,3-diazaspiro[4,4]non-1- ene-4-one and Potassium carbonate were added into reaction mixture. The reaction mixture was heated to reflux. The progress of reaction was checked on HPLC. the reaction mixture was cooled to room temperature and distilled water were added. The aqueous layer was extracted with toluene twice. The combined organic layer was washed with fresh distilled water. The toluene was removed under vacuum. The obtained product was crystallized in isopropanol, and the precipitate was washed with isopropanol and dried.

Example 2: Preparation of 2-n-butyl-3-{[2'-(1-trityl-1H-tetrazol-5-yl) biphen-4-yl] methyl} -1, 3-diazaspiro [4, 4] non-1-ene- 4-one.

Pd(OAC)2 was added to a mixture of triphenyl phosphine in toluene at room temperature. After 10-15 min, Na2SO3 was added and stirred. 2'-(1-trityl-1H-tetrazol)phenylboronic

Page 2 of 3

acid (137.16gm,0.29mol) was added and stirred. Distilled water were added to the reaction mixture. After the solution became clear, 2-butyl-3(4'-bromobenzyl)-1,3- diazaspiro[4,4]non-1-ene-4-one and Potassium carbonate (how much?) was. The reaction mixture was heated to reflux. The progress of reaction was checked on HPLC, then cooled to room temperature, and distilled water were added. The aqueous layer was extracted with toluene twice. The combined organic layer was washed with fresh D.M. water. The toluene was removed under vacuum, and the obtained precipitate was crystallized in isopropanol, washed with isopropanol, and dried.

Example 3: Preparation of (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4- yl]methyl}-1H-imidazol-5-yl)methanol.

Pd(OAC)2 was a...