1-Butanol → 1,7-Dimethyl 4-cyano-4-(3,4-dichlorophenyl)heptanedioate

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Reaction Conditions

Reaction Steps

To a 2-L, three-neck flask equipped with a temperature probe, reflux condenser, addition funnel and overhead stirrer was charged with 3,4-dichlorophenylacetonitrile (100 g, 0.54 mol), methylacrylate (139.56 g, 1.62 mol) and tent-butanol (475 mL). To the mixture was added very slowly (highly exothermic) 1.0 M solution of tetrabutylammonium hydroxide (11 mL, 0.011 mol) in methanol. After the addition was complete, the temperature rose from 21.1° C. to 68.4° C. The resulting clear solution was stirred at 70° C. for 2 h and assayed by TLC (3:7 EtOAc/Heptane; stained using Hanessian solution) and GC. The reaction mixture was cooled to room temperature before being concentrated under reduced pressure. The residue was partitioned between 2 M HCl (500 mL), brine (200 mL) and MTBE (1.5 L). The phases were separated and the aqueous phase was extracted with MTBE (250 mL). The combined organic phases were washed with brine (500 mL), dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure at 40-45° C. to yield the title compound [192.1 g, 99%, 100% (AUC) by GC] as an off-white solid. 1H NMR (DMSO-d6, 300 MHz): δ 7.75 (m, 2H), 7.45 (dd, 1H), 3.5 (s, 6H), 2.4-2.2 (m, 6H), 2.15-1.98 (m, 2H).

Provenance & Evidence