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 449830ノート

反応式

HRID 449830 の反応式
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]

参加物

5

反応物 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

生成物 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 hydrochloride収率 98.8%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-09f1983057dd44f7b120151b8224f3b6
出典データセット
uspto-grants-2013_07
特許番号
US08486943B2

反応ノート

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