Diisopropylamine → (3S,5R)-5-Methyl-3-((4R,5S)-methyl-2-oxo-5-phenyl-oxazolidine-3-carbonyl)-nonanoic acid tert-butyl ester

HRID 28434노트

반응식

HRID 28434 반응식
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C@@H:14]1[C@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:17][C:16](=[O:25])[N:15]1[C:26](=[O:35])[CH2:27][CH2:28][C@H:29]([CH3:34])[CH2:30][CH2:31][CH2:32][CH3:33].Br[CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39]>C1COCC1>[C:41]([O:40][C:38](=[O:39])[CH2:37][C@@H:27]([C:26]([N:15]1[C@H:14]([CH3:13])[C@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:17][C:16]1=[O:25])=[O:35])[CH2:28][C@H:29]([CH3:34])[CH2:30][CH2:31][CH2:32][CH3:33])([CH3:44])([CH3:43])[CH3:42]

참가 물질

6

반응물 4

HCID 7912DiisopropylamineHCID 79177tert-Butyl bromoacetateHCID 57142278(4R,5S)-4-Methyl-3-((R)-4-methyl-octanoyl)-5-phenyl-oxazolidin-2-oneHCID 178418339Butyllithium

생성물 1

HCID 57052159(3S,5R)-5-Methyl-3-((4R,5S)-methyl-2-oxo-5-phenyl-oxazolidine-3-carbonyl)-nonanoic acid tert-butyl ester수율 61%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
10 °C

실험 절차

To a solution of diisopropylamine (1.8 mL, 12.6 mmol) in 30 mL THF at −78° C. was added n-butyllithium (1.6 M soln in hexanes, 7.6 mL, 12.1 mmol), and the mixture stirred 10 minutes at which time (4R, 5S)-4-Methyl-3-((R)-4-methyl-octanoyl)-5-phenyl-oxazolidin-2-one (3.2 g, 10.1 mmol) in 10 mL THF was added dropwise. The solution was stirred for 30 minutes, t-butyl bromoacetate (1.8 mL, 12.1 mmol) was added quickly dropwise at −50° C., and the mixture was allowed to warm slowly to 10° C. over 3 hours. The mixture was partitioned between Et2O and sat. NH4Cl (aq), the phases were separated, and the organic phase dried (MgSO4), and concentrated. The residue was purified by flash chromatography (16:1 to 8:1 hexanes:EtOAc) to provide 2.65 g (61%) of the titled compound as a colorless crystalline solid, mp=84-86° C. [δ]D23+17.1 (c=1.00, CHCl3).

후처리

  1. additionwas added dropwise
  2. customThe mixture was partitioned between Et2O and sat. NH4Cl (aq)
  3. customthe phases were separated
  4. dry with materialthe organic phase dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (16:1 to 8:1 hexanes:EtOAc)

출처 및 근거

ORD 기록
ord-b8a0c67a564f48e5b703263080d9063b
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07419981B2

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