Water → Warfarin alcohol

HRID 2293660Notes

Reaction equation

HRID 2293660 reaction equation
[CH3:1][C:2]([CH2:4][CH:5]([C:12]1[C:21](=[O:22])[O:20][C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]=1[OH:23])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:3].[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C(OCC)C>[OH:23][C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:20][C:21](=[O:22])[C:12]=1[CH:5]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:4][CH:2]([OH:3])[CH3:1]

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 54678486Warfarin

Product 1

HCID 54712717Warfarin alcohol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a milky white suspension of 924 mg of commercially available warfarin in diethyl ether at 0° C. under an argon atmosphere is slowly added 125 mg of lithium aluminum hydride in portions. After 3 hours at 0° C. the reaction is warmed to room temperature. After 1 hour the mixture is re-cooled to 0° C. and slowly treated with 5 mL of water followed by 10 mL of 1N sodium hydroxide. After the bubbling ceases the layers are separated and the aqueous phase is washed with diethyl ether, acidified with 6 N hydrochloric acid, and repeatedly extracted with dichloromethane (methanol-chloroform co-solvents). The combined organic layers are dried (magnesium sulfate) and concentrated under reduced pressure. The residue is flash column chromatographed using 2% to 20% methanol in dichloromethane to afford 590 mg of a diastereomeric mixture of the title product as a white solid.

Workup

  1. temperatureAfter 1 hour the mixture is re-cooled to 0° C.
  2. customare separated
  3. washthe aqueous phase is washed with diethyl ether
  4. extractionrepeatedly extracted with dichloromethane (methanol-chloroform co-solvents)
  5. dry with materialThe combined organic layers are dried (magnesium sulfate)
  6. concentrationconcentrated under reduced pressure
  7. customchromatographed

Sources & evidence

ORD record
ord-9e908ea900d94e6999e952a54fbe9a16
Source dataset
uspto-grants-1997_11
Patent number
US05686486

Reaction notes

Loading…