Potassium Iodide → (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

HRID 449828Notes

Reaction equation

HRID 449828 reaction equation
[CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[NH:11][C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][C@H:31]([OH:34])[C@H:30]1[CH2:35]OS(C)(=O)=O)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][C@H:31]([OH:34])[C@H:30]1[CH2:35][N:11]1[C:12]2[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=2[C:9]2[CH2:8][C@H:7]([NH:6][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[O:21])[CH2:20][C:10]1=2)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 58149374HCID 58149374, compoundHCID 66933207(S)-(7-Cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic Acid Isopropyl Ester

Product 1

HCID 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 esterYield 62.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of ((S)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (1.50 g, 5.29 mmol), (2R,3S)-3-hydroxy-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (3.13 g, 10.59 mmol), cesium carbonate (3.45 g, 10.59 mmol), and potassium iodide (88 mg, 529 μmol) in dimethylformamide (50 mL) is heated in a 60° C. oil bath for two days. After cooling to ambient temperature, the reaction is diluted with ethyl acetate (120 mL) and washed with water (3×100 mL) and brine. The organic portion is dried over sodium sulfate, filtered, and concentrated to dryness. The resulting residue is purified by medium pressure liquid chromatography, eluting with ethyl acetate:chloroform (2:8). Fractions containing pure product are combined and concentrated to afford 1.59 g (62%) of the title compound. LC-ES/MS m/z 505.2 [M+Na]+, TR=3.97 min.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. washwashed with water (3×100 mL) and brine
  3. dry with materialThe organic portion is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe resulting residue is purified by medium pressure liquid chromatography
  7. washeluting with ethyl acetate:chloroform (2:8)
  8. additionFractions containing pure product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c99e88815a2c43548f77441307b295a8
Source dataset
uspto-grants-2013_07
Patent number
US08486943B2

Reaction notes

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