Methanol → 6-cyano-3,5-dihydroxy-N,N-diphenylhexanamide

HRID 1608801Notes

Reaction equation

HRID 1608801 reaction equation
[C:1]([CH2:3][C@@H:4]([OH:24])[CH2:5][C:6](=[O:23])[CH2:7][C:8]([N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:9])#[N:2].CO.COB(CC)CC.[BH4-].[Na+]>O1CCCC1.C(OCC)(=O)C>[C:1]([CH2:3][CH:4]([OH:24])[CH2:5][CH:6]([OH:23])[CH2:7][C:8]([N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:9])#[N:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 522516DiethylmethoxyboraneHCID 4311764Sodium borohydrideHCID 9818592(R)-6-cyano-5-hydroxy-3-oxo-N,N-diphenylhexanamide

Product 1

HCID 224153406-cyano-3,5-dihydroxy-N,N-diphenylhexanamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

Crude (R)-6-cyano-5-hydroxy-3-oxo-N,N-diphenylhexanamide, approximately 0.2 mol, is dissolved in tetrahydrofuran (200 mL) and methanol (100 mL) under a nitrogen atmosphere. The solution is cooled to -20° C., and a 50% solution of methoxydiethylborane in tetrahydrofuran (105 mL) is added. The reaction is cooled to -78° C., and sodium borohydride (24 g, 0.63 mol) is added over 30 minutes. The reaction mixture is maintained at -78° C. for 5 hours, allowed to warm to room temperature, and stand for 10 hours under a nitrogen atmosphere. The reaction is quenched by the addition of acetic acid (40 mL) and concentrated by vacuum distillation to an oil. The residue is dissolved with methanol (400 mL), concentrated by vacuum distillation, redissolved with methanol (300 mL), and reconcentrated by vacuum distillation to give a yellow oil. The oil is taken up in ethyl acetate (300 mL) and washed with deionized water (500 mL). The ethyl acetate solution is concentrated by vacuum distillation to give [R-(R*,R*)])-6-cyano-3,5-dihydroxy-N,N-diphenylhexanamide as an oil which is used without further purification. A small sample is purified by column chromatography on flash silica gel (60:40 hexane:ethyl acetate) as an oil.

Workup

  1. temperatureThe reaction is cooled to -78° C.
  2. temperatureThe reaction mixture is maintained at -78° C. for 5 hours
  3. temperatureto warm to room temperature
  4. customThe reaction is quenched by the addition of acetic acid (40 mL)
  5. concentrationconcentrated by vacuum distillation to an oil
  6. dissolutionThe residue is dissolved with methanol (400 mL)
  7. concentrationconcentrated by vacuum distillation
  8. dissolutionredissolved with methanol (300 mL)
  9. distillationreconcentrated by vacuum distillation
  10. customto give a yellow oil
  11. washwashed with deionized water (500 mL)
  12. concentrationThe ethyl acetate solution is concentrated by vacuum distillation

Sources & evidence

ORD record
ord-01faa164ce114721944c8f59598791c1
Source dataset
uspto-grants-1995_03
Patent number
US05397792

Reaction notes

Loading…