Sodium Carbonate → 2-(3-Amino-4-cyclopropylmethoxy-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester

Participants

Reaction Steps

A mixture of 2-(4-cyclopropylmethoxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (1.85 g, 4.59 mmol) and Pd/C (1.85 g) in ethanol and 1 N HCl (4.60 mL) was hydrogenated under 36 psi H2 in a Parr apparatus. After 4 h, the reaction mixture was filtered through Celite 521®. The filtrate was concentrated under reduced pressure to give a yellow oil. The residue was treated with an aqueous solution of sodium carbonate (3 g in 100 mL of water) and the resulting solution was extracted with ethyl acetate (100 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give a brown oil, which was purified by silica-gel flash chromatography eluting with a gradient of heptane/ethyl acetate (from 10:1 to 2:1) to give 2-(3-amino-4-cyclopropylmethoxy-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (0.88 g, 51%) as a light pink oil: 1HNMR (300 MHz, CDCl3): δ 6.83 (s, 1H), 6.80 (s, 1H), 4.04 (m, 2H), 3.85 (s, 2H), 3.66 (d, 2H, J=6.9 Hz), 3.45 (t, 1H, J=7.8 Hz), 1.84 (m, 1H), 1.49 (m, 1H), 1.39 (m, 1H), 1.22 (m, 1H), 1.14 (t, 3H, J=7.2 Hz), 0.82 (m, 6H), 0.56 (d, 2H, J=7.5 Hz), 0.27 (d, 2H, J=4.5 Hz); 13C NMR (75 MHz, CDCl3): δ 173.61, 142.71, 141.25, 135.51, 123.75 (q, J=30 Hz), 123.52 (q, J=271 Hz), 118.46, 115.52 (q, J=5 Hz), 77.88, 60.70, 49.03, 42.53, 25.86, 22.40, 22.31, 14.07, 10.98, 3.19.

Provenance & Evidence