Acetic Acid → (3R,4R)-3-[(R)-1-phenyl-ethylamino]-piperidine-1,4-dicarboxylic acid 1-tert-butyl Ester 4-ethyl Ester

Participants

Reaction Conditions

Reaction Steps

In a dry flask (R)-5-(1-phenyl-ethylamino)-3,6-dihydro-2H-pyridine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (5.78 g, 15.4 mmol) was dissolved in acetonitrile (25 mL) and glacial acetic acid (25 mL) and cooled to 0° C. Triacetoxyborohydride (9.82 g, 46.3 mmol) was added over a 5-minute period. The reaction mixture was allowed to stir at 0° C. for 2 hours. Concentrated aqueous sodium hydroxide was carefully added to maintain the internal temperature of the flask below 10° C. The resulting solid sodium acetate was filtered and the mixture was extracted with ethyl acetate 3 times (50 mL). The combined organic extracts were dried with magnesium sulfate, filtered, concentrated in vacuo, and then purified by flash chromatography with 20% ethyl acetate in hexanes to give a colorless oil (2.6 g, 47%). The 1H NMR showed a mixture of two rotation isomers. The major compound had the following 1H NMR (300 MHz, CDCl3), δ: 7.28 (t, J=5, 2H), 7.25 (t, J=2, 1H), 7.23 (d, J=4, 2H), 4.35 (m, 2H), 4.24 (q, 2H, J=7), 3.96 (m, 2H), 3.15 (bs, 1H), 2.99 (m, 1H), 2.75 (m, 1H) 2.48 (dt, 2H, J=10, 4), 1.86 (m, 1H), 1.68 (m, 1H), 1.39 (s, 9H), 1.26 (d, 3H, J=6), 1.26 (t, 3H, J=7).

Provenance & Evidence