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

HRID 1527327노트

반응식

HRID 1527327 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([F: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]([F: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 15547566(2R,3S)-1-(tert-Butoxycarbonyl)-3-fluoropyrrolidine-2-carboxylic acid

생성물 1

HCID 68283467(2R,3S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-3-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (2R,3S)-3-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (120 mg, 0.514 mmol) in CH2Cl2 (5 mL) were added successively 3-chloro-2-fluorobenzylamine (0.065 mL, 0.514 mmol), HBTU (293 mg, 0.772 mmol) and DIPEA (0.18 mL, 1.03 mmol), and stirring was continued at RT for 20 h. The reaction mixture was then diluted with CH2Cl2, and the organics were washed with 0.1N aqueous HCl (2×), aqueous NaHCO3 (2×) and brine (1×), dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane gradient 1:4 to 1:3) to afford the title compound as a white foam. TLC Rf (EtOAc/c-hexane 1:1)=0.62; MS (LC/MS): 397 [M+Na]+, 319 [MH−tBu]+, 275 [MH−Boc]+; tR (HPLC conditions b): 4.72 min.

후처리

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

출처 및 근거

ORD 기록
ord-315c2be595ec4c97b6a20472f75362e9
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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