Potassium Cyanide → (3aS,4S,6S,7aR)-6-cyanomethyl-4-(2-methoxyphenyl)-2-[(S)-2-(2-methoxyphenyl)propionyl]perhydroisoindol-4-ol

HRID 1599124Notes

Reaction equation

HRID 1599124 reaction equation
[C-:1]#[N:2].[K+].[CH3:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C@:12]1([OH:45])[CH2:20][C@H:19]([CH2:21]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:18][C@@H:17]2[C@H:13]1[CH2:14][N:15]([C:33](=[O:44])[C@H:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[O:42][CH3:43])[CH3:35])[CH2:16]2>CS(C)=O.O>[C:1]([CH2:21][C@@H:19]1[CH2:18][C@@H:17]2[C@@H:13]([CH2:14][N:15]([C:33](=[O:44])[C@H:34]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[O:42][CH3:43])[CH3:35])[CH2:16]2)[C@@:12]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][CH3:4])([OH:45])[CH2:20]1)#[N:2]

Participants

5

Reactant 2

HCID 9032Potassium CyanideHCID 22884866(3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(S)-2-(2-methoxyphenyl)propionyl]-6-tosyloxymethyl perhydroisoindol-4-ol

Product 1

HCID 9889878(3aS,4S,6S,7aR)-6-cyanomethyl-4-(2-methoxyphenyl)-2-[(S)-2-(2-methoxyphenyl)propionyl]perhydroisoindol-4-olYield 68.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
45 °C

Procedure

1.0 g of potassium cyanide is added to a solution of 5.6 g of (3aS,4S,6R,7aR)-4-(2-methoxyphenyl)-2-[(S)-2-(2-methoxyphenyl)propionyl]-6-tosyloxymethylperhydroisoindol-4-ol in 50 cm3 of dimethyl sulphoxide. After stirring at 45° C. for hours, the reaction mixture is cooled to 20° C., diluted with 300 cm3 of water and then extracted twice with 50 cm3 of ethyl acetate. The organic phase is subsequently washed with 150 cm3 of water, dried. over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.06-0.20 mm, diameter 4.4 cm, height 50 cm), eluting under a pressure of 0.2 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (40:60 by volume) and collecting fractions of 120 cm3. Evaporation to dryness of fractions 11 to 20 under reduced pressure (2.7 kPa) gives 2.9 g of (3aS,4S,6S,7aR)-6-cyanomethyl-4-(2-methoxyphenyl)-2-[(S)-2-(2-methoxyphenyl)propionyl]perhydroisoindol-4-ol in the form of a thick white foam.

Workup

  1. temperaturethe reaction mixture is cooled to 20° C.
  2. extractionextracted twice with 50 cm3 of ethyl acetate
  3. washThe organic phase is subsequently washed with 150 cm3 of water
  4. customdried
  5. concentrationover magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a silica gel column (particle size 0.06-0.20 mm, diameter 4.4 cm, height 50 cm)
  7. washeluting under a pressure of 0.2 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (40:60 by volume)
  8. customcollecting fractions of 120 cm3
  9. customEvaporation to dryness of fractions 11 to 20 under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-1008468202e942fdbcff0c3cced60175
Source dataset
uspto-grants-1998_04
Patent number
US05739351

Reaction notes

Loading…