tert-Butyl bromoacetate → (S)-tert-Butyl 3-((R)-4-benzyl-2-oxooxazolidine-3-carbonyl)hex-5-enoate

HRID 41068ノート

反応式

HRID 41068 の反応式
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][CH2:16][CH:17]=[CH2:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>C1COCC1>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14]([C@@H:15]([CH2:16][CH:17]=[CH2:18])[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[O:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 79177tert-Butyl bromoacetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 10858190(R)-4-Benzyl-3-pent-4-enoyloxazolidin-2-one

生成物 1

HCID 25109987(S)-tert-Butyl 3-((R)-4-benzyl-2-oxooxazolidine-3-carbonyl)hex-5-enoate収率 93%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

A dry round bottom flask was charged with 1a (3.2 g, 12.34 mmol) and dry THF (123 mL) and then cooled to −78° C. To this solution NaHMDS (1M in THF, 13.57 mL, 13.57 mmol) was added over a period of 10 minutes. To ensure complete enolization, the reaction mixture was stirred for an additional 20 minutes at −78° C. A solution of tert-butyl bromoacetate (2.74 mL, 18.51 mmol) in THF (6 mL) was then introduced to the reaction flask. The solution was stirred for 1 hour at −78° C. and then warmed to −48° C. while still stirring. The reaction was monitored by TLC (˜3 h) and quenched with saturated aqueous NH4Cl. The reaction mixture was concentrated by the removing the THF under reduced pressure. The residue was then diluted with dichloromethane. This solution was washed successively with water and brine, dried over Na2SO4, and concentrated under reduced pressure to give white crystals of 2a (4.27 g, 93%). 1H NMR (500 MHz, CDCl3): δ ppm 7.32-7.37 (m, 2H) 7.27-7.30 (m, 3H) 5.74-5.85 (m, 1H) 5.05-5.13 (m, 2H) 4.63-4.70 (m, 1H) 4.25-4.32 (m, 1H) 4.16 (d, J=4.9 Hz, 2H) 3.34 (dd, J=13.4, 2.7 Hz, 1H) 2.74-2.87 (m, 2H) 2.39-2.52 (m, 2H) 2.19-2.26 (m, 1H) 1.44 (s, 9H); 13C NMR (126 MHz, CDCl3): δ 175.0, 171.1, 153.0, 135.6, 134.4, 129.4, 128.8, 127.1, 117.7, 80.6, 65.8, 55.4, 39.0, 37.5, 36.6, 36.1, 28.0. HRMS calcd for C21H27NO5 (M+H) m/z 374.1967, found 374.1971.

後処理

  1. stirringThe solution was stirred for 1 hour at −78° C.
  2. temperaturewarmed to −48° C.
  3. stirringwhile still stirring
  4. customwas monitored by TLC (˜3 h)
  5. customquenched with saturated aqueous NH4Cl
  6. concentrationThe reaction mixture was concentrated by the removing the THF under reduced pressure
  7. additionThe residue was then diluted with dichloromethane
  8. washThis solution was washed successively with water and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-85f3895f5bfe43e0ab48e502372536bb
出典データセット
uspto-grants-2013_09
特許番号
US08530456B2

反応ノート

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