tert-butyl (2S,3S)-2-benzyl-3-hydroxy-5-oxopyrrolidine-1-carboxylate(SALTDATA: FREE) synthesis

Yield:109579-10-4 441 mg

Reaction Conditions:

with sodium tetrahydroborate in methanol at 0 - 20; for 2 h;

Steps:

4.5.16. (2R,3R) or (2S,3S)-tert-Butyl 2-benzyl-3-hydroxy-5-oxopyrrolidine-1-carboxylate (16a and 16b)

To a solution of 1g (656 mg, 1.61 mmol) was stirred in dry THF (10 mL) at room temperature, and then a solution of TBAF (3.2 mL, 1.0 mol in THF) was dropped. The reaction was stirred for 3 h and quenched with water. The mixture was extracted with EtOAc for three times and the combined organic layers were washed with brine. Dried over anhydrous Na₂SO₄, filtered, and concentrated, the residue was purified by chromatography on silica gel to give crude intermediate (468 mg), which contain minor impurity of TBAF. To a solution of oxalyl chloride (0.28 mL, 3.26 mmol) in dry CH₂Cl₂ (10 mL) was dropped DMSO (0.47 mL, 6.53 mmol) over 15 min at -78 °C under argon atmosphere. After being stirred for 30 min, a solution of above crude intermediate (468 mg) in dry CH₂Cl₂ (5.0 mL) was dropped and the mixture was stirred for anther 1 h, then Et₃N (1 mL, 6.96 mmol) was dropped and the mixture was allowed to warm to room temperature. The reaction was quenched with aqueous NaHSO₄ solution (1 M, 30 mL), then the organic layer was separated, and the aqueous phase was extracted with CH₂Cl₂ for two times. The combined organic layers were washed with saturated aqueous solution of NaHSO₄, saturated aqueous NaHCO₃, and brine. Dried, filtered, and concentrated to give crude product 15a or 15b (457 mg, 92%) as a colorless oil without further purification. The above crude mixture of 15a or 15b was dissolved in MeOH (15 mL) and cooled to 0 °C, then NaBH₄ (153 mg, 4.0 mmol) was added in three portions. After being stirred for 2 h at 0 °C to ～room temperature, the reaction was quenched with NaHCO₃ aqueous solution and extracted with DCM for three times. The combined organic layers were concentrated and the residue was purified by chromatography on silica gel to give 16a or 16b (441 mg, yield 96%) as a white solid. Mp 98-99 °C; (2S,3S)-16a +27.7 (c 1.12, CHCl₃); (2R,3R)-16b -28.4 (c 0.8, CHCl₃); IR (film): ν_max 3403, 2975, 1770, 1676, 1366, 1287, 1167 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ 7.30-7.19 (m, 5H), 4.51-4.42 (m, 2H), 3.19-3.09 (m, 2H), 2.60 (dd, J=7.2, 17.0 Hz, 1H), 2.40 (dd, J=7.6, 17.0 Hz, 1H), 1.48 (s, 9H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ=171.8, 149.8, 137.8, 129.9, 129.7, 128.6, 126.7, 83.3, 65.6, 62.7, 40.1, 33.9, 28.0 ppm; MS (ESI): 314 (M+Na⁺); HRMS (ESI) calcd for (C₁₆H₂₁NO₄+Na⁺): 314.1368, found: 314.1372.

References:

Huang, Wei;Ma, Jing-Yi;Yuan, Mu;Xu, Long-Fei;Wei, Bang-Guo [Tetrahedron,2011,vol. 67,# 40,p. 7829 - 7837] Location in patent:experimental part