Ammonium formate → (R)-2-(5-hydroxy-indol-1-yl)-propionic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of (R)-2-(5-benzyloxy-indol-1-yl)-propionic acid methyl ester (20.0 g, 0.065 mol) and palladium hydroxide (2.0 g, wet 20% Pd on carbon) in ethanol (340 mL) under argon was heated to 40° C. To this suspension was slowly added a solution of ammonium formate (5.04 g, 0.078 mol) in ethanol/water (110.5/9.6 mL). Fifteen percent (15%) of the solution was added initially over a period of 40 minutes to ensure that the reaction had initiated (indicated by reverse phase HPLC). The remaining solution was then slowly added over a period of 1.5 h. The reaction was monitored by reverse phase HPLC. Upon completion, the reaction mixture was cooled to rt and filtered through a silica gel pad. The pad was washed with ethanol. The combined fractions were concentrated to dryness under vacuum at 30° C. The crude product was purified by silica gel chromatography using a gradient of 5-35% ethyl acetate/hexanes to give 14.00 g (98%) of (R)-2-(5-hydroxy-indol-1-yl)-propionic acid methyl ester as an oil. Chiral HPLC indicated an ee value of the desired enantiomer as 95%. 1H NMR (400 MHz, DMSO-d6) δ 8.7 (s, 1H), 7.3 (s, 1H), 7.1 (d, 1H), 6.8 (s, 1H), 6.61 (d, 1H), 6.28 (d, 1H), 5.32 (q, 1H), 3.60 (s, 3H), 1.70 (d, 3H); LC/MS (+esi) m/z 220.1 (M+H)+, RT 2.07 min.

Provenance & Evidence