Sodium borohydride → HCID 86759428, compound

HRID 2086552Notes

Reaction equation

HRID 2086552 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@@H:16]([O:26][CH2:27][C:28](OC)=[O:29])[C:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)=[O:18])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[BH4-].[Na+]>CO>[F:32][C:2]([F:1])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][CH:16]([O:26][CH2:27][CH2:28][OH:29])[CH:17]([OH:18])[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 12990864HCID 12990864, compound

Product 1

HCID 86759428HCID 86759428, compoundYield 33.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 25 mg of (2-R)-2-((R)-1-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-2-(methoxycarbonylmethoxy)-4′-fluoroacetophenone (higher Rf ester diastereomer) from Example 1 in 1 ml of methanol was added 4 mg of sodium borohydride at room temperature. The reaction was stirred for 16 h and was then quenched 18% aqueous citric acid. HPLC on a reverse phase phenyl column (gradient of 65% A: 35%B to 10% A: 90% B over 50 min, A=10 mM ammonium acetate in water: B=7.2 mM ammonium acetate in 92.8% acetonitrile/7.2% methanol) of the reaction mixture indicated a 4:1 ratio of diastereomeric diol products (Rt=23 and 24 min). The reaction was diluted with water and extracted twice with ethyl acetate. The organic layers were each washed with brine, dried over sodium sulfate, combined and evaporated. Prep TLC (60% ethyl acetate/hexanes) afforded 8 mg of title compound as a 4:1 mixture of diastereomers.

Workup

  1. customwas then quenched 18% aqueous citric acid
  2. waitHPLC on a reverse phase phenyl column (gradient of 65% A: 35%B to 10% A: 90% B over 50 min
  3. customa 4:1 ratio of diastereomeric diol products (Rt=23 and 24 min)
  4. additionThe reaction was diluted with water
  5. extractionextracted twice with ethyl acetate
  6. washeach washed with brine
  7. dry with materialdried over sodium sulfate
  8. customevaporated

Sources & evidence

ORD record
ord-0d6a476ef6554b7e83bb8f7d10c45cec
Source dataset
uspto-grants-2004_04
Patent number
US06727244B2

Reaction notes

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