Diisopropylamine → t-Butyl 3-(1-benzyloxymethylimidazol-2-yl)-3-hydroxy-4-methyl-pentanoate

HRID 3144

反応式

HRID 3144 の反応式
[CH:1](NC(C)C)([CH3:3])[CH3:2].[Li][CH2:9][CH2:10][CH2:11][CH3:12].[C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH3:14].CN(P(N(C)C)(N(C)C)=O)C.C(OC[C:41]1[N:42]=[C:43]([C:46](=[O:50])[CH:47]([CH3:49])[CH3:48])[NH:44][CH:45]=1)C1C=CC=CC=1.[C:51]([O-])([O-])=[O:52].[K+].[K+]>C1COCC1>[CH2:9]([O:52][CH2:51][N:42]1[CH:41]=[CH:45][N:44]=[C:43]1[C:46]([OH:50])([CH:47]([CH3:48])[CH3:49])[CH2:14][C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:10]1[CH:3]=[CH:1][CH:2]=[CH:12][CH:11]=1

参加物

8

反応物 6

HCID 7912DiisopropylamineHCID 10908tert-Butyl acetateHCID 11430Potassium CarbonateHCID 12679HexamethylphosphoramideHCID 178418339ButyllithiumHCID 178418343HCID 178418343、化合物

生成物 1

HCID 18934556t-Butyl 3-(1-benzyloxymethylimidazol-2-yl)-3-hydroxy-4-methyl-pentanoate収率 90%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-10 °C

実験手順

Diisopropylamine (83 μL, 0.59 mmol) and THF (1.5 mL) were cooled to -40° C. and n-BuLi (188 μL, 0.47 mmol, 2.5M in hexane) was added. The reaction mixture was warmed to -10° C. and stirred for 15 m, recooled to -70° C. and t-butyl acetate (63 μL, 0.47 mmol) was added. The reaction was stirred for 5 m, and HMPA (254 μL, 1.41 mmol) was added. The reaction was stirred at -70° C. for 5 m and 1-(benzyloxymethylimidazol-2-yl)-2-methyl-propan-1-one (100 mg, 0.39 mmol) in THF (1.5 mL) was added dropwise. The mixture was stirred at -70° C. for 30 m, -40° C. for 30 m, -10° C. for 30 m, warmed to 23° C., poured into 10% aqueous K2CO3 and extracted with EtOAc. The combined organic extracts were washed with brine, dried (K2CO3), concentrated and flash chromatographed (silica gel, step gradient, 0-20% EtOAc/hexanes) to afford the title compound (131 mg, 90%). 1H NMR(CDCl3, 400 MHz) δ 7.25 (m, 5H), 6.96 (s, 1H), 6.91 (s, 1H), 5.69 (d, 1H, J=10 Hz), 5.65 (d, 1H, J=10 Hz), 4.53 (d, 1H, J=11 Hz), 4.48 (d, 1H, J=11 Hz), 3.23 (d, 1H, J=6 Hz), 2.57 (d, 1H, J=6 Hz), 2.14 (m, 1H), 1.39 (s, 9H); 0.97 (d, 3H, J=7 Hz), 0.75 (d, 3H, J=7 Hz); MS(ES) m/e 375 [M+H]+.

後処理

  1. customrecooled to -70° C.
  2. additionwas added
  3. additionwas added dropwise
  4. stirringThe mixture was stirred at -70° C. for 30 m, -40° C. for 30 m, -10° C. for 30 m
  5. temperaturewarmed to 23° C.
  6. extractionextracted with EtOAc
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried (K2CO3)
  9. concentrationconcentrated
  10. customflash chromatographed (silica gel, step gradient, 0-20% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-af96ced584d54df9885b41c24ce0e973
出典データセット
uspto-grants-1998_03
特許番号
US05733882

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