Lithium Hydroxide → [(S)-7-Cyano-4-((2R,3R)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester hydrochloride

HRID 449830노트

반응식

HRID 449830 반응식
C(OC([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13]C(=O)C[Cl:16])[C@H:9]1[CH2:18][N:19]1[C:27]2[CH:26]=[CH:25][C:24]([C:28]#[N:29])=[CH:23][C:22]=2[C:21]2[CH2:30][C@H:31]([NH:33][C:34]([O:36][CH:37]([CH3:39])[CH3:38])=[O:35])[CH2:32][C:20]1=2)=O)(C)(C)C.[Li+].[OH-]>CO.C(OCC)(=O)C>[ClH:16].[CH:37]([O:36][C:34](=[O:35])[NH:33][C@@H:31]1[CH2:32][C:20]2[N:19]([CH2:18][C@@H:9]3[C@H:10]([OH:13])[CH2:11][CH2:12][NH:8]3)[C:27]3[CH:26]=[CH:25][C:24]([C:28]#[N:29])=[CH:23][C:22]=3[C:21]=2[CH2:30]1)([CH3:39])[CH3:38]

참가 물질

5

반응물 2

HCID 3939Lithium HydroxideHCID 86651083(2R,3R)-3-(2-Chloro-acetoxy)-2-((S)-7-cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 66933117[(S)-7-Cyano-4-((2R,3R)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester hydrochloride수율 98.8%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of (2R,3R)-3-(2-chloro-acetoxy)-2-((S)-7-cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 894.4 μmol) in MeOH (2 mL) is treated with 2 N LiOH solution (2 mL) and the suspension is stirred for 4 h at room temperature. The suspension is diluted with ethyl acetate (60 mL) and washed with water and brine. The organic portion is dried over sodium sulfate, filtered, and concentrated. The residue (0.39 g) is dissolved in 10 mL of MeOH (10 mL) and treated with 4 N HCl in 1,4-dioxane solution (10 mL). The solution is stirred for 2 h and concentrated in vacuo to afford 0.37 g (92%) of the title compound. LC-ES/MS m/z 383.2 [M+H]+, TR=1.86 min.

후처리

  1. washwashed with water and brine
  2. dry with materialThe organic portion is dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue (0.39 g) is dissolved in 10 mL of MeOH (10 mL)
  6. additiontreated with 4 N HCl in 1,4-dioxane solution (10 mL)
  7. stirringThe solution is stirred for 2 h
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-09f1983057dd44f7b120151b8224f3b6
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486943B2

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