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SYNTHESIS OF (R)-ETHYL-3-AMINO-4-(2,4,5-TRIFLUOROPHENYL) BUTANOATE OXALATE

IP.com Disclosure Number: IPCOM000194647D
Publication Date: 2010-Apr-06
Document File: 2 page(s) / 90K

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SYNTHESIS OF
(R)-ETHYL-3-AMINO-4-(2,4,5-TRIFLUOROPHENYL) BUTANOATE OXALATE

(R)-ethyl-3-amino-4-(2,4,5-trifluorophenyl) butanoate of the following formula

F

F

is an intermediate in the process for the preparation of (3R)-3-amino-1-[9-(trifluoromethyl)- 1,4,7,8-tetrazabicyclo[4.3.0]nona-6,8-dien-4-yl]-4-(2,4,5- trifluorophenyl)butan-1-one phosphate, which is a glucagon-like peptide 1 metabolism modulator, hypoglycemic agent, and dipeptidyl peptidase IV inhibitor.

Provided is a process for preparing (R)-ethyl-3-amino-4-(2,4,5-trifluorophenyl) butanoate oxalate:

3-Amino-4-(2,4,5-trifluorophenyl)but-2-enoic acid ethyl ester was hydrogenated using (Ru(COD)Cl and R-BINAP) in the presence of 2,2,2-trifluoroethanol to obtain (R)-ethyl-3- amino-4-(2,4,5-trifluorophenyl) butanoate. The reaction mixture of was evaporated under reduce pressure to obtain 61 g of oily residue. (R)-Ethyl-3-amino-4-(2,4,5-trifluorophenyl) butanoate oily residue was dissolved in 2-propanol (700 ml). The reaction mixture was heated to 45-55 oC

and 26.7 g oxalic acid dehydrate (portion vise) was added. Suspension was stirred for 1 hour at 45-55 oC and then was heated to reflux and stirred for 30 minutes. The solution was cooled to 20- 25 oC during 1 hour and stirred for 1 hour at 20-25 oC.

The product was collected by vacuum filtration, washed with 2-propanol (100 ml) and dried at 40-45 oC under vacuum. The obtained product was (R)-ethyl-3-amino-4-(2,4,5-trifluorophenyl) butanoate oxalate (52 g, 88....