Methyl iodide → HCID 86755236, compound

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (0.691 ml, 4.93 mmol) in anhydrous tetrahydrofuran (10 ml) was cooled to -78° C. prior to the dropwise addition of 1.6M butyllithium (2.57 ml, 4.11 mmol) via a syringe. The solution was warmed to 0° C. and then immediately recooled to -78° C., whereupon a solution of compound (8) from Example 2 (600 mg, 1.64 mmol) in tetrahydrofuran (10 ml) was added dropwise via a cannula. Stirring was continued for 1 hour at -78° C. followed by the rapid injection of methyl iodide (0.512 ml, 8.22 mmol). The reaction mixture was allowed to warm slowly to room temperature overnight (16 hours) after which the solvent was evaporated. The residue was partitioned between ethyl acetate (50 ml) and brine (25 ml) and the organic layer was dried (magnesium sulphate), filtered and evaporated to yield a yellow oil. This was purified by flash chromatography on silica gel [ethyl acetate/petroleum ether (1:49)] affording the title compound (51) in 94% diastereoisomeric excess (Rf 0.25) as a colourless oil (406 mg, 65%). δH (300 MHz, CDCl3) 7.41-7.17 (10H, m, Ph), 5.93-5.79 (1H, m, NCH2CH=CH2), 5.11 (1H, app. dd, J=17.3 and 1.3, trans CH=CH2), 5.08 (1H, app. dd, J=10.1 and 1.1, cis CH=CH2), 4.18 (1H, d, J=11.4, PhCHCH3), 3.29 (1H, app. ddt, J=14.7, 5.0 and 1.9, NCH2), 3.19 (1H, dq, J=11.4 and 6.9, CHCHCH3), 3.10 (1H, dd, J=14.7 and 8.0, NCH2), 1.50 (9H, s, (CH3)3C), 0.94 (3H, d, J=6.7, PhCHCH3), 0.90 (3H, d, J=6.9, CHCHCH3).

Provenance & Evidence