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

HRID 470796ノート

反応式

HRID 470796 の反応式
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]

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 241Benzene溶媒

実験手順

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).

後処理

  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]

出典と根拠

ORDレコード
ord-52402b2bc93847d6b296c7db6249f8fa
出典データセット
uspto-grants-2014_01
特許番号
US08629167B2

反応ノート

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