Triethylborane → Methyl (3R,5S,E)-7-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-3,5-dihydroxy-6-heptenoate

HRID 2050588Notes

Reaction equation

HRID 2050588 reaction equation
C(B(CC)CC)C.C(B(CC)OC)C.[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:23]=[C:24]([CH:46]([CH3:48])[CH3:47])[N:25](/[CH:34]=[CH:35]/[C@@H:36]([OH:45])[CH2:37][C:38](=[O:44])[CH2:39][C:40]([O:42][CH3:43])=[O:41])[C:26]=2[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:18][CH:17]=1.[BH4-].[Na+]>C(OCC)(=O)C.CO.C1COCC1>[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:23]=[C:24]([CH:46]([CH3:48])[CH3:47])[N:25](/[CH:34]=[CH:35]/[C@@H:36]([OH:45])[CH2:37][C@@H:38]([OH:44])[CH2:39][C:40]([O:42][CH3:43])=[O:41])[C:26]=2[C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 7357TriethylboraneHCID 522516DiethylmethoxyboraneHCID 4311764Sodium borohydrideHCID 14849791methyl (5S,E)-7-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-5-hydroxy-3-oxo-6-heptenoate

Product 1

HCID 14849841Methyl (3R,5S,E)-7-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-3,5-dihydroxy-6-heptenoateYield 48.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of dry THF (4 ml) and dry methanol (1 ml) under nitrogen at room temperature was treated with a solution of triethylborane (1.0M in THF, 0.6 ml). After 1 h, the mixture was cooled to -78°, and a portion of this diethyl methoxyborane solution (1.93 ml) was added to methyl (5S,E)-7-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-5-hydroxy-3-oxo-6-heptenoate (73.8 mg) under magnetic stirring. The homogeneous solution was stirred for 1 h, then treated with powdered sodium borohydride (98%, 6.4 mg) at -78°. After 4.5 h, the reaction mixture was diluted with ethyl acetate, quenched with saturated aqueous ammonium chloride solution and allowed to warm to room temperature overnight. The organic solution was separated and the aqueous solution washed with ether (3×). The combined organic solutions were dried and evaporated. The residue was azeotroped with methanol (3×) to give a brown gum. This gum was subjected to preparative t.l.c. eluting with System A (3:2), to give the title compound (36.1 mg) as a brown gum, [α]D20 +5.38° (c 1.86, ethyl acetate), δ(CDCl3) 1.40 (d, J 7 Hz, 6H, --CH(CH3)2), 1.4-1.8 (m, 2H, CH(OH)CH2CH(OH)), 2.44 (d, J 5 Hz, 2H, CH2CO2CH3), 3.13 (septet, J 7 Hz, 1H, --CH(CH3)2), 3.73 (s, 3H, OCH3), 3.85 (broad s, 2H, CH(OH)CH2CH(OH)), 4.15 (m, 1H, CH(OH)CH2CO2CH3), 4.42 (m, 1H, =CHCH(OH)CH2), 5.31 (dd, J 15 and 5 Hz, 1H, NCH=CH--), 6.66 (dd, J 15 and 2 Hz, 1H, NCH=CH--), 6.90 (t, J 9 Hz, 2H, C-3 and C-5 protons of 4-(4-fluorophenyl)), 7.09 (t, J 9 Hz, 2H, C-3 and C-5 protons of 5-(4-fluorophenyl)), 7.23 and 7.39 (2 dd, J 9 and 6 Hz, 4H, C-2 and C-6 protons of 4-fluorophenyls).

Workup

  1. temperaturethe mixture was cooled to -78°
  2. waitAfter 4.5 h
  3. customquenched with saturated aqueous ammonium chloride solution
  4. customThe organic solution was separated
  5. washthe aqueous solution washed with ether (3×)
  6. customThe combined organic solutions were dried
  7. customevaporated
  8. customThe residue was azeotroped with methanol (3×)
  9. customto give a brown gum
  10. washeluting with System A (3:2)

Sources & evidence

ORD record
ord-895ac18065c24ee897eb093914224532
Source dataset
uspto-grants-1991_05
Patent number
US05013749

Reaction notes

Loading…