Thiazole, 4-(1-Methylethyl)- synthesis

Yield:17626-74-3 70%

Reaction Conditions:

in 1,4-dioxane at 110; for 0.25 h;

Steps:

15

1-Bromo-3-methyl-butan-2-one (1.15 g, 6.95 mmol) and thioformamide ( 0.43 g, 6.95 mmol) were dissolved in dioxane (10 ml.) and heated in microwave at 110 °C for 15 min. Dichloromethane and NaHCO₃ was added and after separation the organic phase was washed with NaOH (aq, 1 M) and water. Back-extracted water phase with dichloromethane. The combined organic phases were washed with water and brine, dried over Na₂SO₄, filtered and evaporated to yield 0.82g (70%) of 4- isopropyl-1 ,3-thiazole. EPO 4-lsopropyl-1 ,3-thiazole (0.62 g, 4.9 mmol) was dissolved in methyl-f-butyl ether (15 ml.) and the solution was cooled to 0°C. Addition of isopropyl magnesium chloride (2.9 ml_, 2.0 M) was done drop wise at 0⁰C. The mixture was then heated to 40⁰C and sulfur dioxide in dimethoxyethane (0.79 ml_, 7.7 M) was added drop wise and the reaction was then left at this temperature for 45 min. After cooling the reaction mixture to 0°C, Λ/-chlorosuccinimide (0.97 g, 7.3 mmol) was added, and the reaction were kept at 0°C for 1 h. After addition of HCI (aq, 0.2 M, 10 ml.) at 0⁰C the reaction was left to warm up to ambient temperature for 2 hrs and extracted with methyl-f-butylether. The organic phase was washed with of HCI (aq, 0.2 M), water and brine then dried over Na₂SO₄, filtered and evaporated to yield 0.92 g (84%) of product.

References:

WO2006/64286,2006,A1 Location in patent:Page/Page column 121-122