Allyl bromide → HCID 19874769, compound

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (0.075 ml, 0.53 mmol) in dry tetrahydrofuran (0.5 ml) is cooled to 0° C. and a 2.5M solution of n-butyllithium in hexane is added (0.19 ml, 0.47 mmol). The solution is stirred at 0° C. for 15 minutes and then cooled down to -78° C. A solution of 3-benzyloxypropyl 2-[(3-benzyloxypropyl)oxy]acetate (0.165 g 0.44 mmol) in tetrahydrofuran (1 ml) is added slowly. The mixture is allowed to stir at -78° for 1 hour and then hexamethyl phosphoramide (0.5 ml) is added, followed by allyl bromide (0.23 ml, 2.7 mmol). The mixture is allowed to warm to room temperature over 3 hours and then quenched using saturated aqueous ammonium chloride. The mixture is extracted with ether (3×15 ml) and the combined organic extracts are washed with water (3×45 ml) and brine (30 ml). The organic layer is dried, evaporated and the residue purified by flash chromatography on silica gel using ethyl acetate/hexane (1:4) as eluent to obtain 3-benzyloxypropyl 2-[(3-benzyloxypropyl)oxy]pent-4-enoate. IR (CH2Cl2): 1745, 1644, 1195, 1101 cm-1. Reduction of the ester with diisobutyl aluminum hydride, followed by conversion of the alcohol as previously described yields methyl 4-[(3-benzyloxypropyl)-oxy]-hept-6-enoate. This is in turn converted to methyl 4-[3-(N-t-butoxycarbonyl-p-chlorophenylsulfonamido)-propyloxy]-7-(3-pyridyl)-heptanoate as starting material for compound under (a), or methyl 4-[3-(N-t-butoxycarbonyl-p-chlorophenylsulfonamido)-propyloxy]-6-(3-pyridyloxy)-hexanoate for compound under (b), according to methods described in the previous examples.

Provenance & Evidence