Tosylmethyl isocyanide → 5-Cyano-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid dimethylamide

HRID 1961582Notes

Reaction equation

HRID 1961582 reaction equation
[CH3:1][N:2]([CH3:14])[C:3]([N:5]1[CH2:9][CH:8]2[CH2:10][C:11](=O)[CH2:12][CH:7]2[CH2:6]1)=[O:4].C1(C)C=CC(S([CH2:24][N+:25]#[C-])(=O)=O)=CC=1.CC(C)([O-])C.[K+]>COCCOC.C(O)(C)(C)C.O.[Cl-].[Na+].O>[CH3:1][N:2]([CH3:14])[C:3]([N:5]1[CH2:9][CH:8]2[CH2:10][CH:11]([C:24]#[N:25])[CH2:12][CH:7]2[CH2:6]1)=[O:4]

Participants

8

Reactant 3

HCID 161915Tosylmethyl isocyanideHCID 23665647Potassium tert-butoxideHCID 59151531N,N-Dimethyl-5-oxo-hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide

Product 1

HCID 686261915-Cyano-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid dimethylamideYield 51.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 80711,2-DimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

N,N-dimethyl-5-oxo-hexahydro-cyclopenta[c]pyrrole-2-carboxamide 1g (12.9 g, 0.066 mol) and 4-toluenesulfonylmethyl isocyanide (14.2 g, 0.0727 mol) were dissolved in 240 mL of 1,2-dimethoxyethane with stirring upon cooling by an ice-water bath, followed by dropwise addition of a solution of potassium tert-butoxide (14.8 g, 0.132 mol) in tert-butanol. Upon completion of the addition, the ice-water bath was removed. The reaction mixture was warmed up to room temperature and reacted overnight. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was diluted with 100 mL of water and 50 mL of saturated brine and extracted with ethyl acetate (200 mL×3). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 5-cyano-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid dimethylamide 12a (7.0 g, yield 51%) as a light yellow oil.

Workup

  1. temperatureupon cooling by an ice-water bath
  2. additionUpon completion of the addition
  3. customthe ice-water bath was removed
  4. customreacted overnight
  5. extractionextracted with ethyl acetate (200 mL×3)
  6. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6bfe915e8cf24b2588d31cd7404479e8
Source dataset
uspto-grants-2013_04
Patent number
US08415349B2

Reaction notes

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