Sodium hydride → HCID 19823659, compound

Participants

Reaction Steps

A solution of the product of Example 142 (28.1 g) in tetrahydrofuran (60 ml) was added under argon to a stirred suspension of sodium hydride (5.04 g of a 50% dispersion in mineral oil) in tetrahydrofuran (30 ml) at <30° C. After 45 minutes dimethylformamide (10 ml) was added the mixture stirred for 16 hours at ambient temperature. The mixture was cooled to below 10° C. and a solution of chloroacetylmorpholine (18 g) in tetrahydrofuran (60 ml) added. The mixture was then stirred at ambient temperature for 21/2 days and then poured into water. The aqueous mixture was extracted with ether and the extract dried and evaporated to give a residue which was distilled. The residue after distillation was dissolved in hot petroleum ether (bp 80° to 100° C.), treated with charcoal, filtered and cooled. The supernatant was decanted from an oily residue and evaporated to give an oil which was distilled on a Buchi Kugelrohr apparatus (140°/0.2 mm) leaving 2-{4-[1-(4-chlorophenyl)cyclobutyl]-4-dimethylaminobutoxy}-N,N-3-oxapentamethyleneacetamethyleneacetamide as the residue. A solution of this product (4.18 g) in ether (20 ml) was added dropwise over 15 minutes under argon to a stirred mixture of ether (10 ml) and a 1.55M solution of methyllithium in ether (7 ml) at -20° to -25° C. The mixture was stirred for 3 hours at ambient temperature and then cooled to below -20° C. and a saturated aqueous solution of ammonium chloride (40 ml) was added. The ether phase was separated, dried and evaporated to give an oil which was purified by flash chromatography using ether as the eluant to give 1-{4-[1-(4-chlorophenyl)cyclobutyl] -4-dimethylaminobutoxy}propan-2-one as an oil the boiling point of which was not determined.

Provenance & Evidence