反应详情

温度

0 °C

A solution of BocTyrOH (5.30 g, 18.8 mmol) and methyl iodide (2.57 mL, 41.4 mmol) in 80 mL of dry THF was cooled at 0° C. and sodium hydride (60% dispersion, 2.47 g, 62.0 mmol) was added. The reaction was allowed to stir at 0° C. for 1 hour, then at rt overnight. Excess sodium hydride was quenched by the dropwise addition of 10 mL of THF/H2O (1:1) and the solvents were removed in vacuo. After removal of the solvents, the deep orange gel was diluted with 30 mL of water and washed with pentane (2×30 mL). The aqueous phase was acidified with solid citric acrd (pH 2). Ethyl acetate was used for extraction. The combined extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The crude residue was purified by silica gel column chromatography eluting with ethyl ether to afford the desired compound as a yellow oil (5.22 g, 90%); [α]29 D-15.7° (c 1.0, MeOH), Lit.14b[α]22 D-16.9° (c 1.0, MeOH) 1H NMR 300 MHz, CDCl3) δ 7.18 & 7.12 (2H, two d), 6.85 (2H,d), 4,58 (1H, two t), 3.80 (3H, s), 3.24 & 3.13 (1H, 2dd), 2.76 & 2.68 (3H, 2s), 1.43 & 1.38 (9H, 2s); FABMS 619.3 (2M+H), 310.2 (M+H), 210.2 (M−Boc); HRFABMS Calcd for C16H24MO5 (M+H) 310.1654, Found 310.1648.

1. customat rt
2. customovernight
3. customExcess sodium hydride was quenched by the dropwise addition of 10 mL of THF/H2O (1:1)
4. customthe solvents were removed in vacuo
5. customAfter removal of the solvents
6. additionthe deep orange gel was diluted with 30 mL of water
7. washwashed with pentane (2×30 mL)
8. extractionEthyl acetate was used for extraction
9. washThe combined extracts were washed with brine
10. dry with materialdried (MgSO4)
11. concentrationconcentrated in vacuo
12. customThe crude residue was purified by silica gel column chromatography
13. washeluting with ethyl ether