Methanol → Dodecanoic acid, 12-bromo-, methyl ester

Participants

Reaction Conditions

Reaction Steps

12-Bromododecanoic acid (10 g, 35.8 mmol) was stirred with methanol (60 ml) and Toluene (180 ml). Trimethyl orthoformate (38 g, 358 mmol) and Amberlyst A-15 (ca. 1 g) were added. The reaction was mixed for 16 h. At some point the heating unit failed, So the reaction cooled from 70° C. to rt. The solution was heated to 70° C. and mixed for 24 h. TLC (2:1 heptane/AcOEt) indicated the reaction was incomplete. Trimethyl orthoformate (38 g, 358 mmol) and Amberlyst A-15 (1.4 g) were added, and the solution was stirred at 70° C. for 16 h. The sample was concentrated under vacuum to yield a brown oil (9.87 g). Vacuum distillation at 0.09 torr yielded two fractions of colorless oil (109-117° C., 6.95 g; 117-129° C., 1.17 g). These were combined and dissolved in AcOEt (100 ml) and washed with Sat. NaHCO3 (2×40 ml), dried over MgSO4 and concentrated under vacuum. The oil was dissolved in 20:1 AcOEt/TEA (10 ml) and added to a bed of silica (3 cm×7.5 cm dia). The column was eluted with AcOEt/TEA 20:1 (200 ml), and the filtrate was concentrated under vacuum. The oil was dissolved in AcOEt (100 ml) and washed with 1 N HCl (2×40 ml), dried over MgSO4 and concentrated under vacuum to yield a colorless oil (7.52 g, 72% yield).

Provenance & Evidence