Hydrochloric Acid → [(S)-7-Cyano-4-((2R,3S)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester

HRID 449840Notes

Reaction equation

HRID 449840 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[C@H:9]1[CH2:14][N:15]1[C:23]2[CH:22]=[CH:21][C:20]([C:24]#[N:25])=[CH:19][C:18]=2[C:17]2[CH2:26][C@H:27]([NH:29][C:30]([O:32][CH:33]([CH3:35])[CH3:34])=[O:31])[CH2:28][C:16]1=2)=O)(C)(C)C.Cl>CO.O1CCOCC1>[CH:33]([O:32][C:30](=[O:31])[NH:29][C@@H:27]1[CH2:28][C:16]2[N:15]([CH2:14][C@@H:9]3[C@@H:10]([OH:13])[CH2:11][CH2:12][NH:8]3)[C:23]3[CH:22]=[CH:21][C:20]([C:24]#[N:25])=[CH:19][C:18]=3[C:17]=2[CH2:26]1)([CH3:35])[CH3:34]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66933249(2R,3S)-2-((S)-7-Cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66933386[(S)-7-Cyano-4-((2R,3S)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl]-carbamic acid isopropyl esterYield 96%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (2R,3S)-2-((S)-7-cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (0.50 g, 1.04 mmol) in methanol (20 mL) is treated with 4 N hydrogen chloride in 1,4-dioxane (20 mL), stirred at room temperature for 3 h and concentrated. The residue is suspended in ethyl acetate (200 mL) and treated with 2 N aqueous sodium hydroxide solution (20 mL). The organic layer is washed with brine, dried over sodium sulfate, and concentrated. The resulting residue is purified by medium pressure liquid chromatography, eluting with methanol:chloroform (5:95). Fractions containing pure product are combined and concentrated to afford 0.38 g (96%) of the title compound. LC-ES/MS/MS m/z 383.2 [M+H]+, TR=1.86 min.

Workup

  1. concentrationconcentrated
  2. additiontreated with 2 N aqueous sodium hydroxide solution (20 mL)
  3. washThe organic layer is washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe resulting residue is purified by medium pressure liquid chromatography
  7. washeluting with methanol:chloroform (5:95)
  8. additionFractions containing pure product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-4c6cebf89f1f4a75880df4681c815429
Source dataset
uspto-grants-2013_07
Patent number
US08486943B2

Reaction notes

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