methyl 5-amino-2-cyanobenzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Thionyl chloride (3.9 ml, 5.3 mmol) was added dropwise to a solution of (2R)-3-bromo-2-hydroxy-2-methylpropionic acid (8.19 g, 44.8 mmol, prepared as described in WO 2005/000794) in 190 ml of THF and 5.8 ml of N,N-dimethyl-acetamide (DMAC) at 5° C. under nitrogen atmosphere. The solution was stirred for 3 h at room temperature. A solution of 5-amino-2-cyanobenzoic acid methyl ester (7.50 g, 4.3 mmol) in 75 ml of THF was added and the reaction mixture was maintained at 50° C. for 3 h and at room temperature for 16 h. The mixture was poured into water, extracted with ethyl acetate, washed with water, dried over Na2SO4 and evaporated under reduced pressure. The crude product was stirred in toluene and filtration afforded the purified compound. the reaction mixture was maintained at 50° C. for 3 h and at room temperature for 16 h extracted with ethyl acetate washed with water dried over Na2SO4 evaporated under reduced pressure The crude product was stirred in toluene filtration afforded the purified compound

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The mixture of 5-amino-2-bromobenzoic acid methyl ester (14.27 g, 62.0 mmol) and CuCN (6.11 g, 68.2 mmol) in DMF (130 ml) was heated at 150° C. for 1 h 10 min under nitrogen atmosphere. The mixture was cooled to 70° C. and poured into the mixture of water (250 ml) and 12.5% NH3 (500 ml). The product was extracted into ethyl acetate (3×250 ml). The organic phase was washed several times with 12.5% NH3 and water, dried over Na2SO4 and concentrated under vacuum. The mixture was cooled to 70° C. The product was extracted into ethyl acetate (3×250 ml) The organic phase was washed several times with 12.5% NH3 and water dried over Na2SO4 concentrated under vacuum