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

HRID 501745ノート

反応式

HRID 501745 の反応式
[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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-269e3815802b46a9aee43abbc56143ae
出典データセット
uspto-grants-2010_08
特許番号
US07772221B2

反応ノート

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