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

Participants

Reaction Steps

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).

Provenance & Evidence