Lithium Hydroxide → Cbz-3,5-Dichloro-L-Phenylalanine

HRID 501745노트

반응식

HRID 501745 반응식
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[C:20]([Cl:25])[CH:19]=1)[C:13]([O:15]C)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-]>C1COCC1>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:17][C:18]1[CH:19]=[C:20]([Cl:25])[CH:21]=[C:22]([Cl:24])[CH:23]=1)[C:13]([OH:15])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

4

반응물 2

HCID 3939Lithium HydroxideHCID 68464283(S)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)propanoate

생성물 1

HCID 68465047Cbz-3,5-Dichloro-L-Phenylalanine

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

Step BF (3): To a solution of (S)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)propanoate (20.60 g, 53.94 mmol) in THF was added 2M LiOH (250 mL). After the reaction was stirred at rt for 18 h, the THF was removed in vacuo. The pH was adjusted to below two by 6M HCl. The mixture was extracted three times into EtOAc, and the combined organic layers were dried with MgSO4. Concentration in vacuo afforded pure (S)-2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)propanoic acid. This material was taken up in methylene chloride (250 mL), and p-nitrophenol (7.50 g, 53.94 mmol) was added. EDC was added portionwise (12.43 g, 64.73 mmol), followed by Hunig's base (11.3 mL, 64.73 mmol). The reaction was allowed to stir at rt for 80 h. The reaction was extracted 3 times with 1M HCl, then with brine. The reaction was next extracted with 0.5M NaOH (yellow color formed), and again with brine. The organic layer was dried with MgSO4, and concentrated to a yellow gum. Silica gel chromatography (EtOAc/hexane gradient) afforded (S)-4-nitrophenyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)propanoate (26.37 g, 58% yield).

후처리

  1. customthe THF was removed in vacuo
  2. extractionThe mixture was extracted three times into EtOAc
  3. dry with materialthe combined organic layers were dried with MgSO4
  4. concentrationConcentration in vacuo

출처 및 근거

ORD 기록
ord-269e3815802b46a9aee43abbc56143ae
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772221B2

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