反応 #11266

反応方程式

methyl ester

(2S)-4,4-Difluoro-3,3-dimethyl-N-(Boc)proline methyl ester

LiOH

→

(2S)-4,4-Difluoro-3,3-dimethyl-N-(Boc)proline

溶媒

methanol

water

反応条件

後処理

1. 1
   その他The methanol was removed in vacuo
2. 2
   workup.ADDITIONthe remaining solution was diluted with water (200 mL)
3. 3
   抽出The aqueous solution was extracted with ether (2×200 mL)
4. 4
   抽出extracted again with ether (2×200 mL)
5. 5
   洗浄The combined organics were washed with brine (1×200 mL)
6. 6
   乾燥dried with magnesium sulfate
7. 7
   濃縮concentrated in vacuo
8. 8
   その他The while solid was dried overnight at 40° C. under vacuum
9. 9
   その他Isolated yield: 4.3 g (95%)

実験手順

To a solution of methyl ester F4 (4.7 g, 16 mmol) in methanol (100 mL) was added a solution of LiOH (6.8 g, 160 mmol) in water (50 mL) and the solution was heated at 50° C. for 14 h. The methanol was removed in vacuo and the remaining solution was diluted with water (200 mL). The aqueous solution was extracted with ether (2×200 mL), acidified with 1N HCl (200 mL) and extracted again with ether (2×200 mL). The combined organics were washed with brine (1×200 mL), dried with magnesium sulfate and concentrated in vacuo. The while solid was dried overnight at 40° C. under vacuum. Isolated yield: 4.3 g (95%). 1H NMR (400 MHz, DMSO-d6): □ 12.95 (bs, 1H), 3.93 (s, 1H), 3.84–3.74 (m, 2H), 1.38 (s)+1.33 (s) (9H), 1.19 (s, 3H), 1.01 (s, 3H); 19F NMR (376 MHz, DMSO-d6): □ −111.4 (dt, J=227, 13 Hz)+−112.4 (dt, J=227, 13 Hz) (1F), −113.5 (dt, J=227, 14 Hz) +−113.9 (dt, J=227, 15 Hz) (1F); MS-APCI (m/z+): 180.1, (m/z−): 278.

出典