反应详情

To a stirred solution of methyl 4-[(2S,4S)-1-tert-butoxycarbonyl-4-hydroxy-2-pyrrolidinyl]methoxybenzoate (2.10 g, 5.98 mmol) in THF (60 ml) was added 60% oil NaH (359 mg, 8.97 mmol) at 0° C. After 15 minutes stirring, MeI (1.20 ml, 8.97 mmol) was added to the mixture was added at same temperature, and the resulting mixture was allowed to raise to room temperature for over 1 h. Then 60% oil NaH (359 mg, 8.97 mmol) and MeI (1.20 ml, 8.97 mmol) was added to the reaction mixture at room temperature and stirred for 14 h. The reaction mixture was poured into ice water and extracted with CHCl3. The combined extracts were washed with aq. NaHCO3 and brine. After dried over Na2SO4, the extracts were concentrated in vacuo. The residue was chromatographed on silica gel [50 g, n-hexane/EtOAc(4/1)], to give methyl 4-[(2S,4S)-1-tert-butoxycarbonyl-4-methoxy-2-pyrrolidinyl]methoxybenzoate (1.32 g, 60%) as a colorless oil. 1H-NMR (CDCl3) δ 1.48 (s, 9H), 2.05 (m, 1H), 2.29 (d, J=14.2 Hz, 1H), 3.30 (s, 3H), 3.36–4.38 (m, 4H), 6.76 (br, 2H), 7.97 (d, J=8.8 Hz, 2H).

1. additionwas added at same temperature
2. stirringstirred for 14 h
3. extractionextracted with CHCl3
4. washThe combined extracts were washed with aq. NaHCO3 and brine
5. dry with materialAfter dried over Na2SO4
6. concentrationthe extracts were concentrated in vacuo
7. customThe residue was chromatographed on silica gel [50 g, n-hexane/EtOAc(4/1)]