Sodium Cyanide → (R)-tert-butyl 2-(cyanomethyl)-4,4-difluoropyrrolidine-1-carboxylate

HRID 1754401Notes

Reaction equation

HRID 1754401 reaction equation
CS(O[CH2:6][C@@H:7]1[CH2:11][C:10]([F:13])([F:12])[CH2:9][N:8]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])(=O)=O.[C-:21]#[N:22].[Na+]>CS(C)=O>[C:21]([CH2:6][C@@H:7]1[CH2:11][C:10]([F:13])([F:12])[CH2:9][N:8]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])#[N:22]

Participants

4

Reactant 2

HCID 8929Sodium CyanideHCID 86704454((S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidin-2-yl)methyl methanesulfonate

Product 1

HCID 86704455(R)-tert-butyl 2-(cyanomethyl)-4,4-difluoropyrrolidine-1-carboxylateYield 76%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A DMSO (40 ml) solution of ((S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidin-2-yl)methyl methanesulfonate and NaCN (1.59 g, 3.24 mmol) was stirred at 45° C. for 4 hours and at 50° C. for 2 days, the progress of the reaction was monitored by LC-MS. After cooling to room temperature, the reaction was quenched by the addition of water (˜60 ml). Reaction mixture was extracted with EtOAc (˜40 ml), two layers were separated, organic layer was washed with brine (˜25 ml), the extraction and wash sequence was repeated for two more times. Organic layers were combined, dried (Na2SO4), filtered, solvent was removed in vacuo. Product was purified by silica gel chromatography (Hexane/EtOAc, gradient from 100:0 to 80:20). Compound (R)-tert-butyl 2-(cyanomethyl)-4,4-difluoropyrrolidine-1-carboxylate was obtained as a colorless oil: 2.10 g (76% yield over 2 steps).

Workup

  1. customthe reaction was quenched by the addition of water (˜60 ml)
  2. customReaction mixture
  3. extractionwas extracted with EtOAc (˜40 ml), two layers
  4. customwere separated
  5. washorganic layer was washed with brine (˜25 ml)
  6. extractionthe extraction
  7. washwash sequence
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customsolvent was removed in vacuo
  11. customProduct was purified by silica gel chromatography (Hexane/EtOAc, gradient from 100:0 to 80:20)

Sources & evidence

ORD record
ord-ba0951c34c9040199057eebfb136ce92
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

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