Methanol → HCID 86749406, compound

HRID 2295187Notes

Reaction equation

HRID 2295187 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:11]=[C:10]([CH:20]([CH3:22])[CH3:21])[C:9]=2/[CH:23]=[CH:24]/[CH:25]([OH:34])[CH2:26][C:27](=[O:33])[CH2:28][C:29]([O:31][CH3:32])=[O:30])=[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[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:11]=[C:10]([CH:20]([CH3:21])[CH3:22])[C:9]=2/[CH:23]=[CH:24]/[C@@H:25]([OH:34])[CH2:26][C@@H:27]([OH:33])[CH2:28][C:29]([O:31][CH3:32])=[O:30])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7357TriethylboraneHCID 4311764Sodium borohydrideHCID 86749405HCID 86749405, compound

Product 1

HCID 86749406HCID 86749406, compoundYield 89.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (E)-7-[4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinyl]-5-hydroxy-3-oxo-6-heptenoic acid, methyl ester (357 mg, 0.77 mmol) in THF (12 ml) was treated with triethylborane (1.0M in THF, 1.62 ml, 1.62 mmol). Twenty five 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 (29.4 mg, 0.78 mmol) followed by dropwise addition of dry methanol (1.90 ml). After stirring at -78° C. for 1.5 hours, the mixture was quenched with 30% H2 O2 (3.5 ml) in H2O (11 ml). The mixture was kept at -78° C. for 15 minutes, then warmed to room temperature and stirred for 30 minutes. The solution was poured into 50% saturated NaHCO3 and extracted with Et2O (3×). The Et2O extracts were combined, washed with H2O, saturated NaHCO3 and brine, then dried (Na2SO4). Filtration and removal of the solvent gave a yellow oil which was chromatographed (Flash, Merck SiO2, 40% EtOAc in hexane) to afford (3R, 5S, 6E)-7-[4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinyl]-3,5-dihydroxy-6-heptenoic acid, methyl ester (320 mg, 89%) as a colorless oily foam.

Workup

  1. customTwenty five milliliters of air was bubbled through the solution
  2. temperatureThe solution was cooled to -78° C.
  3. stirringAfter stirring at -78° C. for 1.5 hours
  4. customthe mixture was quenched with 30% H2 O2 (3.5 ml) in H2O (11 ml)
  5. waitThe mixture was kept at -78° C. for 15 minutes
  6. temperaturewarmed to room temperature
  7. stirringstirred for 30 minutes
  8. additionThe solution was poured into 50% saturated NaHCO3
  9. extractionextracted with Et2O (3×)
  10. washwashed with H2O, saturated NaHCO3 and brine
  11. dry with materialdried (Na2SO4)
  12. filtrationFiltration and removal of the solvent
  13. customgave a yellow oil which
  14. customwas chromatographed (Flash, Merck SiO2, 40% EtOAc in hexane)

Sources & evidence

ORD record
ord-a60b9d07564f4dffb13bc5f0342aa6ae
Source dataset
uspto-grants-1997_11
Patent number
US05691322

Reaction notes

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