4-Methylmorpholine → [(R)-1-(3,5-Dichloro-4-fluoro-phenylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester

HRID 449152

反応式

HRID 449152 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[Cl:29][C:30]1[CH:31]=[C:32]([NH2:38])[CH:33]=[C:34]([Cl:37])[C:35]=1[F:36]>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([C:10](=[O:12])[NH:38][C:32]1[CH:31]=[C:30]([Cl:29])[C:35]([F:36])=[C:34]([Cl:37])[CH:33]=1)[CH3:13])([CH3:2])([CH3:3])[CH3:4]

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 759483,5-Dichloro-4-fluoroanilineHCID 637606BOC-D-alanine

生成物 1

HCID 67390502[(R)-1-(3,5-Dichloro-4-fluoro-phenylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
20 °C

実験手順

To a cooled (−20° C.) solution of (R)-2-tert-butoxycarbonylamino-propionic acid (57.2 g, 302 mmol) in anhydrous THF (582 mL) was added N-methyl-morpholine (34.9 mL, 317 mmol) at a rate to keep the internal temperature at −15° C. Isobutyl chloroformate (42.0 mL, 317 mmol) was then added over a 20 min period and the resulting mixture was stirred for 30 min. A solution of 3,5-dichloro-4-fluoro-phenylamine (54.4 g, 302 mmol) in THF (160 mL) was then added over 40 min. The reaction mixture was warmed to 20° C. and stirred for 20 h. The reaction mixture was filtered and concentrated in vacuo. To the resulting oil was added MeOH (200 mL) and the solution was concentrated to provide the title compound as a tan colored solid, m/z 295.3 [M-t-Bu]+. This material was used without further purification.

後処理

  1. customat −15° C
  2. stirringstirred for 20 h
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated in vacuo
  5. additionTo the resulting oil was added MeOH (200 mL)
  6. concentrationthe solution was concentrated

出典と根拠

ORDレコード
ord-96938e9745c44d4e9167bfb93995cfb4
出典データセット
uspto-grants-2013_07
特許番号
US08481750B2

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