Acetic Acid → HCID 18661335, compound

Participants

Reaction Conditions

Reaction Steps

Ethyl (S,S)-2-[1'-(carboxybenzylamino)ethyl]-4-pentenoate (2.19 g, 7.18 mmol) is dissolved in MeOH (50 ml) and the resulting solution cooled to -78° C. O3, from a Welsbach ozonator set at the standard settings, is bubbled through the reaction mixture until starting material can no longer be detected by thin-layer chromatography (2:1 hexane: EtOAc). Dimethyl sulfide (5 ml) is added to the reaction mixture which is allowed to warm to room temperature and is then concentrated by rotary evaporation. The crude aldehyde is dissolved in methanol (25 ml) and tetrahydrofuran (25 ml) and the resulting solution is cooled to 0° C. under a nitrogen atmosphere. Benzyl amine (4.06 ml, 37.15 mmol) followed by acetic acid (4.68 ml, 81.73 mmol) is added to the reaction mixture which is then stirred at 0° C. for 12 min. NaCNBH3 (0.95 g, 14.86 mmol) is added to the reaction mixture which is allowed to warm to room temperature and continuously stirred for a 24 hour period. The reaction mixture is adjusted to pH 9 with 1N NaOH and the resulting mixture is partitioned between EtOAc and water. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic layers are dried over MgSO4, filtered and then concentrated by rotary evaporation. The crude product is purified by chromatography (1:1 hexane: EtOAc) to give (S,S)-1-benzyl-2-oxo-3-[1'(carboxybenzylamino)ethyl]pyrrolidine: 1H NMR (300 MHz, CDCl3) δ 1.30 (d, J is 7 Hz, 3H), 1.77 (ddd, J is 16, 12, 9 Hz, 1H), 2.04 (m, 1H), 2.59 (ddd, J is 9, 9, 4 Hz, 1H), 3.04-3.09 (m, 2H), 3.95 (m, 1H), 4.34 (s, 2H), 5.01 (s, 2H), 5.11 (broad s, 1H), 7.10-7.28 (m, 10H).

Provenance & Evidence