Methanol → HCID 86749413, compound

HRID 1720708Notes

Reaction equation

HRID 1720708 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13](/[CH:14]=[CH:15]/[CH:16]([OH:25])[CH2:17][C:18](=[O:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21])=[C:12]([CH:26]([CH3:28])[CH3:27])[CH:11]=[C:10]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:9]=2)=[CH:4][CH:3]=1.C(B(CC)CC)C.[BH4-].[Na+].CO>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:13]([CH:14]=[CH:15][CH:16]([OH:25])[CH2:17][CH:18]([OH:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21])=[C:12]([CH:26]([CH3:28])[CH3:27])[CH:11]=[C:10]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7357TriethylboraneHCID 4311764Sodium borohydrideHCID 86749412HCID 86749412, compound

Product 1

HCID 86749413HCID 86749413, compoundYield 86.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (E)-7-[2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]-5-hydroxy-3-oxo-6-heptenoic acid, methyl ester (182 mg, 0.39 mmol) in THF (5.5 ml) was treated with triethylborane (1.0N in THF, 830 ul, 0.83 mmol). Twenty milliliters of air was bubbled through the solution and the mixture was stirred at room temperature for 30 minutes. The solution was cooled to -78° C. and treated with NaBH4 (15.0 mg, 0.40 mmol) followed by dropwise addition of dry methanol (0.9 ml). After stirring at -78° C. for 1.75 hours, the mixture was quenched with 30% H2O2 (2.8 ml) in H2O (6 ml). The mixture was kept at -78° C. for 15 minutes, then warmed to room temperature and stirred for 45 minutes. The solution was poured into 50% saturated NaHCO3 and extracted with Et2O (2×). The combined Et2O extracts were washed with saturated NaHCO3, H2O, and brine, then dried (Na2SO4), filtered and stripped. Purification of the resulting oil (flash, Merck SiO2, 50% EtOAc in hexane) gave (3R*, 5S*, 6E)-7-[2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]-3,5-dihydroxy-6-heptenoic acid, methyl ester (157 mg, 86%) as a colorless oily foam.

Workup

  1. customTwenty milliliters of air was bubbled through the solution
  2. temperatureThe solution was cooled to -78° C.
  3. stirringAfter stirring at -78° C. for 1.75 hours
  4. customthe mixture was quenched with 30% H2O2 (2.8 ml) in H2O (6 ml)
  5. waitThe mixture was kept at -78° C. for 15 minutes
  6. temperaturewarmed to room temperature
  7. stirringstirred for 45 minutes
  8. additionThe solution was poured into 50% saturated NaHCO3
  9. extractionextracted with Et2O (2×)
  10. washThe combined Et2O extracts were washed with saturated NaHCO3, H2O, and brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. customPurification of the resulting oil (flash, Merck SiO2, 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-958743094df84c47b46826c1598567c3
Source dataset
uspto-grants-1996_04
Patent number
US05506219

Reaction notes

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