Sodium hydride → [(R)-1-(2-cyanocyclopropyl)-ethyl]-carbamic acid tert-butyl ester

HRID 246219Notes

Reaction equation

HRID 246219 reaction equation
[I-].[CH3:2][S+](C)C.[H-].[Na+].[C:8]([O:12][C:13](=[O:21])[NH:14][C@H:15]([CH3:20])[CH:16]=[CH:17][C:18]#[N:19])([CH3:11])([CH3:10])[CH3:9]>CS(C)=O.O.C(OCC)(=O)C>[C:8]([O:12][C:13](=[O:21])[NH:14][C@@H:15]([CH:16]1[CH2:2][CH:17]1[C:18]#[N:19])[CH3:20])([CH3:11])([CH3:9])[CH3:10]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 75127Trimethylsulfonium iodideHCID 86677956((R)-3-cyano-1-methyl-allyl)-carbamic acid tert-butyl ester

Product 1

HCID 71280072[(R)-1-(2-cyanocyclopropyl)-ethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

DMSO was added to trimethylsulfonium iodide (1.79 g, 8.15 mmol) and sodium hydride (60% in mineral oil, 326 mg, 8.15 mmol) at 0° C. Then a 3:1 E:Z mixture of ((R)-3-cyano-1-methyl-allyl)-carbamic acid tert-butyl ester (0.4 g, 2.04 mmol) in DMSO was added. The reaction mixture was left to warm up to room temperature overnight. The reaction was stirred at room temperature for 2 days then diluted with water and ethyl acetate. The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 20% to 50% EtOAc in hexanes) to provide [(R)-1-(2-cyanocyclopropyl)-ethyl]-carbamic acid tert-butyl ester as two discreet diastereomers (arbitrarily assigned). Diastereomer A (250 mg, 58%) as a colorless oil; MS: (M+H)+=211. Diastereomer B (130 mg, 30%) as a white powder; M+Na)+=233.

Workup

  1. additionwas added
  2. waitThe reaction mixture was left
  3. dry with materialThe organic layers were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (silica gel, 80 g, 20% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-469560e05c6649c6873fb6cd8d9cc3db
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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