Phosphorus oxychloride → 2-Chloro-4-((1R,2S)-2-hydroxy-1-(5-phenyloxazol-2-yl)propylamino)-3-methylbenzonitrile

HRID 470796노트

반응식

HRID 470796 반응식
P(Cl)(Cl)(Cl)=O.[Si]([O:13][C@@H:14]([CH3:39])[C@@H:15]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[C:31]([Cl:37])[C:30]=1[CH3:38])[C:16]([NH:18][CH2:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=O)(C(C)(C)C)(C)C>C1C=CC=CC=1>[Cl:37][C:31]1[C:30]([CH3:38])=[C:29]([NH:28][C@@H:15]([C:16]2[O:27][C:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:19][N:18]=2)[C@@H:14]([OH:13])[CH3:39])[CH:34]=[CH:33][C:32]=1[C:35]#[N:36]

참가 물질

4

반응물 2

HCID 24813Phosphorus oxychlorideHCID 57908587(2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-N-(2-oxo-2-phenylethyl)butanamide

생성물 1

HCID 442011212-Chloro-4-((1R,2S)-2-hydroxy-1-(5-phenyloxazol-2-yl)propylamino)-3-methylbenzonitrile수율 4%

시약·촉매·용매 1

HCID 241Benzene용매

실험 절차

A 100 mL, round bottomed flask was charged with phosphorous oxychloride (0.5 mL, 5.24 mmol) and benzene (20 mL). (2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-N-(2-oxo-2-phenylethyl)butanamide (1.14 g, 2.28 mmol) was then added to the mixture which was then placed under reflux for 4 h. The mixture was then concentrated en vacuo, then partitioned between EtOAc (40 mL) and a saturated solution of sodium bicarbonate (30 mL). The organic layer was washed with water (20 mL), dried (Na2SO4). Purification by flash column chromatography [hexanes/Et2O (3:2) as eluent] afforded the title compound as a white solid (30 mg, 4% yield). 1H NMR (500 MHz, CDCl3, δ in ppm) 7.59 (d, J=8 Hz, 2H), 7.32-7.42 (m, 4H), 7.28 (s, 1H), 6.58 (d, J=8 Hz, 1H), 5.17 (d, J=7 Hz, 1H), 4.93-4.95 (m, 1H), 4.66-4.75 (m, 1H), 2.40 (s, 3H) and 1.63 (d, J=6 Hz, 3H).

후처리

  1. temperatureunder reflux for 4 h
  2. concentrationThe mixture was then concentrated en vacuo
  3. custompartitioned between EtOAc (40 mL)
  4. washThe organic layer was washed with water (20 mL)
  5. dry with materialdried (Na2SO4)
  6. customPurification by flash column chromatography [hexanes/Et2O (3:2) as eluent]

출처 및 근거

ORD 기록
ord-52402b2bc93847d6b296c7db6249f8fa
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629167B2

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