Acetone Cyanohydrin → (R)-1-Boc-3-cyanopyrrolidine

HRID 1601020Notes

Reaction equation

HRID 1601020 reaction equation
C1[CH2:11][CH2:10][N:9]2[C:4](=[N:5][CH2:6][CH2:7][CH2:8]2)CC1.[CH3:12][C:13]([CH3:17])([OH:16])[C:14]#N.C(OCC)(=[O:20])C>C(#N)C>[C:13]([O:16][C:4]([N:9]1[CH2:10][CH2:11][C@@H:7]([C:6]#[N:5])[CH2:8]1)=[O:20])([CH3:17])([CH3:14])[CH3:12]

Participants

5

Reactant 3

HCID 6406Acetone CyanohydrinHCID 8857Ethyl AcetateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene

Product 1

HCID 7018344(R)-1-Boc-3-cyanopyrrolidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The compound (12.2 g) obtained in (7) was dissolved in anhydrous acetonitrile (122 ml). To the solution, 1,8-diazabicyclo[5,4,0]-7-undecene (8.02 ml) and acetone cyanohydrin (6.53 ml) were added, followed by heating under reflux for 10 hours. The reaction mixture was diluted with ethyl acetate (1 liter) and washed five times with water (200 ml) and once with a saturated aqueous solution of ammonium chloride (200 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure, whereby the crude product (9.10 g) was obtained. The resulting crude product was purified by column chromatography (eluent: benzene/ethyl acetate=17/1), whereby (3R)-1-tert-butoxycarbonyl-3-cyanopyrrolidine (4.41 g) was obtained.

Workup

  1. temperatureby heating
  2. temperatureunder reflux for 10 hours
  3. washwashed five times with water (200 ml)
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated by evaporation under reduced pressure, whereby the crude product (9.10 g)
  6. customwas obtained
  7. customThe resulting crude product was purified by column chromatography (eluent: benzene/ethyl acetate=17/1)

Sources & evidence

ORD record
ord-c32e7ae5ee0341c3a42d1a97012a5e47
Source dataset
uspto-grants-1999_11
Patent number
US05977097

Reaction notes

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