Methanol → methyl (E)-7-[3-(4-fluorophenyl)bicyclo[3.2.1]oct-2-en-2-yl]-3,5-dihydroxy-hept-6-enoate

HRID 982062Notes

Reaction equation

HRID 982062 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:14][CH:13]3[CH2:15][CH:10]([CH2:11][CH2:12]3)[C:9]=2/[CH:16]=[CH:17]/[CH:18]([OH:27])[CH2:19][C:20](=[O:26])[CH2:21][C:22]([O:24][CH3:25])=[O:23])=[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[CH2:14][CH:13]3[CH2:15][CH:10]([CH2:11][CH2:12]3)[C:9]=2/[CH:16]=[CH:17]/[CH:18]([OH:27])[CH2:19][CH:20]([OH:26])[CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7357TriethylboraneHCID 4311764Sodium borohydrideHCID 14677528methyl (E)-7-[3-(4-fluorophenyl)bicyclo[3.2.1]oct-2-en-2-yl]-5-hydroxy-3-oxohept-6-enoate

Product 1

HCID 14677529methyl (E)-7-[3-(4-fluorophenyl)bicyclo[3.2.1]oct-2-en-2-yl]-3,5-dihydroxy-hept-6-enoateYield 46.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of methyl (E)-7-[3-(4-fluorophenyl)bicyclo [3.2.1]oct-2-en-2-yl]-5-hydroxy-3-oxohept-6-enoate (2.85 g, 7.65 mmoles) in 12 ml anhydrous THF was added triethylborane (11.5 ml of a 1M THF solution, 11.5 mmoles). The mixture was stirred for 5 minutes and cooled to -78° C. Sodium borohydride (0.333 g, 8.8 mmoles) was added followed by the dropwise addition of 5 ml methanol. The mixture was stirred for 60 minutes and quenched with the dropwise addition of aqueous H2O2 (12 ml of 30% H2O2 in 27 ml H2O). The mixture was warmed to 25° C. during 90 minutes and poured into a mixture of ethyl acetate and aqueous HCl. The organic layer was washed with water and brine and dried (MgSO4). Removal of the volatiles in vacuo provided a residue which was purified by HPLC using 60% hexanes in ethyl acetate. The product rich fractions were concentrated in vacuo and provided 1.32 g of the oily product.

Workup

  1. stirringThe mixture was stirred for 60 minutes
  2. customquenched with the dropwise addition of aqueous H2O2 (12 ml of 30% H2O2 in 27 ml H2O)
  3. temperatureThe mixture was warmed to 25° C. during 90 minutes
  4. additionpoured into a mixture of ethyl acetate and aqueous HCl
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. customRemoval of the volatiles in vacuo
  8. customprovided a residue which
  9. customwas purified by HPLC
  10. concentrationThe product rich fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-caba36ad5fde4e63a2234c18510639b0
Source dataset
uspto-grants-1991_02
Patent number
US04994494

Reaction notes

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