Hydrochloric Acid → benzhydryl (2R)-hydroxy-4-phenylbutyrate

HRID 129437

Reaction equation

HRID 129437 reaction equation
[OH:1][C@H:2]([CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:3]([O:5]CC)=[O:4].[OH-].[Li+].Cl.[C:19]1([C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[N+]=[N-])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CO>[OH:1][C@H:2]([CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:3]([O:5][CH:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 612301,1'-(Diazomethylene)bis(benzene)HCID 2733848Ethyl (R)-2-hydroxy-4-phenylbutyrate

Product 1

HCID 54145254benzhydryl (2R)-hydroxy-4-phenylbutyrateYield 38.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dissolve (R)-2-hydroxy-4-phenylbutyric acid, ethyl ester (4.16 g, 20 mmol) in methanol (40 mL). Add 1N lithium hydroxide (25 mL, 25 mmol) and stir under an atmosphere of argon for 3.5 hours. Acidify with 1N hydrochloric acid (25 mL), saturate with sodium chloride and extract with ethyl acetate (3×25 mL). Combine the organic phases, dry (MgSO4) and evaporate the solvent in vacuo. Take up the residue in methylene chloride (20 mL) and add diphenyldiazomethane (3.36 g, 17.3 mmol). Stir overnight and wash with saturated sodium hydrogen carbonate (2×). Dry (MgSO4), evaporate the solvent in vacuo and recrystallize (methylene chloride/hexane then again with cyclohexane) to give (R)-2-hydroxy-4-phenylbutyric acid, diphenylmethyl ester as white needles (2.3 g, 38%); mp 82°-84° C.

Workup

  1. concentrationsaturate with sodium chloride
  2. extractionextract with ethyl acetate (3×25 mL)
  3. dry with materialCombine the organic phases, dry (MgSO4)
  4. customevaporate the solvent in vacuo
  5. stirringStir overnight
  6. washwash with saturated sodium hydrogen carbonate (2×)
  7. dry with materialDry (MgSO4)
  8. customevaporate the solvent in vacuo
  9. customrecrystallize (methylene chloride/hexane

Sources & evidence

ORD record
ord-7cd04a2268294779af6c1635fa2f3163
Source dataset
uspto-grants-1995_11
Patent number
US05468745

Linked notes

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