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

HRID 1040513

반응식

HRID 1040513 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
20 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-a7931d5a3b814b88afaeffe96e4f2fc3
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08552205B2

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