Diisopropylethylamine → (2S,3S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1527336노트

반응식

HRID 1527336 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[C:19]([F:26])=[C:20]([CH:23]=[CH:24][CH:25]=1)[CH2:21][NH2:22].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[C@H:9]1[C:14](=[O:16])[NH:22][CH2:21][C:20]1[CH:23]=[CH:24][CH:25]=[C:18]([Cl:17])[C:19]=1[F:26])=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2773614(3-Chloro-2-fluorophenyl)methanamineHCID 14037017(2S,3S)-1-(tert-Butoxycarbonyl)-3-hydroxypyrrolidine-2-carboxylic acid

생성물 1

HCID 68283845(2S,3S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (2S,3S)-3-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (800 mg, 3.46 mmol; prepared according to J. Amer. Chem. Soc. 2005, 127, 15923-15932) in CH2Cl2 (35 mL) were added successively 3-chloro-2-fluorobenzylamine (0.435 mL, 3.46 mmol), HBTU (1.97 g, 5.19 mmol), DIPEA (1.21 mL, 6.92 mmol). After stirring at RT for 18 h, the reaction mixture was diluted with CH2Cl2 and the organics were washed with water (2×), 0.1N aqueous HCl (2×), aqueous NaHCO3 solution (2×) and brine, dried (phase separator) and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:2 to 4:1 then EtOAc) to afford the title compound as a colorless wax. TLC Rf (EtOAc/c-hexane 1:1)=0.32; MS (LC/MS): 373 [M+H]+, 395 [M+Na]+, 767 [2M+Na]+; tR (HPLC conditions C): 4.42 min.

후처리

  1. washthe organics were washed with water (2×), 0.1N aqueous HCl (2×), aqueous NaHCO3 solution (2×) and brine
  2. customdried (phase separator)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash column chromatography on silica gel (EtOAc/c-hexane 1:2 to 4:1

출처 및 근거

ORD 기록
ord-506968c25dd24d689a7aed8b5ad839eb
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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