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

HRID 1527331ノート

反応式

HRID 1527331 の反応式
[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]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2773614(3-Chloro-2-fluorophenyl)methanamineHCID 15547565(2R,3R)-1-(tert-Butoxycarbonyl)-3-fluoropyrrolidine-2-carboxylic acid

生成物 1

HCID 68284018(2R,3R)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-3-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (2R,3R)-3-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (45.0 mg, 0.193 mmol) in CH2Cl2 (5 mL) were added successively 3-chloro-2-fluorobenzylamine (0.024 mL, 0.193 mmol), HBTU (110 mg, 0.289 mmol) and DIPEA (0.067 mL, 0.386 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 (eluent: EtOAc/c-hexane gradient 1:4 to 1:3) to afford the title compound. TLC Rf (EtOAc/c-hexane 1:1)=0.31; MS (LC/MS): 397 [M+Na]+, 319 [MH−tBu]+, 275 [MH−Boc]+; tR (HPLC conditions b): 4.37 min.

後処理

  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 (eluent: EtOAc/c-hexane gradient 1:4 to 1:3)

出典と根拠

ORDレコード
ord-189d76b0e81649cb88b157c8669df4d8
出典データセット
uspto-grants-2015_07
特許番号
US09085555B2

反応ノート

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