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 449830Notes

Reaction equation

HRID 449830 reaction equation
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]

Participants

5

Reactant 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

Product 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 hydrochlorideYield 98.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-09f1983057dd44f7b120151b8224f3b6
Source dataset
uspto-grants-2013_07
Patent number
US08486943B2

Reaction notes

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