Diisopropylethylamine → (S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(3-chlorophenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate

HRID 1480539노트

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HRID 1480539 반응식
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:23])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CO[CH:35]1[N:39]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:38]([CH3:48])([CH3:47])[CH2:37][CH2:36]1>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:23])[C@H:15]([C@H:35]1[N:39]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:38]([CH3:48])([CH3:47])[CH2:37][CH2:36]1)[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 59564912HCID 59564912, 화합물HCID 66845068HCID 66845068, 화합물

생성물 1

HCID 66846240(S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(3-chlorophenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate수율 62.9%

시약·촉매·용매 2

HCID 24193Titanium Tetrachloride촉매HCID 6344Dichloromethane용매2회

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온도
-78 °C

실험 절차

A solution of (R)-4-benzyl-3-(2-(3-chlorophenyl)acetyl)oxazolidin-2-one (0.975 g, 2.96 mmol) in dry DCM (125 mL) was cooled to −78° C., and TiCl4 (3.10 mL, 3.10 mmol) was added. DIEA (0.566 mL, 3.25 mmol) was added to this stirring cold solution for 15 minutes. A solution of tert-butyl 5-methoxy-2,2-dimethylpyrrolidine-1-carboxylate (0.881 g, 3.84 mmol) in DCM (20 mL) was added to the cold mixture. The reaction was stirred for 15 minutes at −78° C. and then warmed to −10° C. (ice/acetone) and stirred for 3 hours. The reaction was quenched with NH4Cl, diluted with DCM (50 mL), water (50 mL), and the layers were separated. The aqueous layer was extracted with DCM (25 mL), dried (MgSO4) and concentrated to an oil. TLC (10% ethyl acetate/hexanes) shows desired product at Rf˜0.2. Purification by flash chromatography (5% ethyl acetate/hexanes-10% ethyl acetate/hexanes) gave (S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(3-chlorophenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate (0.98 g, 1.86 mmol, 62.9% yield). HPLC, 254 nm, 100% purity, retention time=3.86 minutes.

후처리

  1. stirringstirred for 3 hours
  2. customThe reaction was quenched with NH4Cl
  3. additiondiluted with DCM (50 mL), water (50 mL)
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with DCM (25 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated to an oil
  8. customPurification by flash chromatography (5% ethyl acetate/hexanes-10% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-fb6d28890d424f60932955f9385096b9
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409886B2

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