Thiazole → HCID 67258520, compound

Participants

Reaction Conditions

Reaction Steps

Thiazole (21.3 g, 250 mmol) in THF (160 mL) was cooled to −70° C. and then n-BuLi (100 mL, 250 mmol) was added slowly over 5 minutes, keeping the temperature at −60° C. or lower. The resulting slurry was stirred for 45 minutes at this temperature and then the product of Step 1 (48.55 g, 228 mmol) in THF (50 mL) was added dropwise, maintaining the temperature at −60° C. The solution was stirred for one hour and then the cooling bath removed. At −20° C., 2M HCl (114 mL) was added and upon warming to RT the homogeneous solution was diluted with EtOAc (150 mL). The phases were separated and the aqueous layer was extracted with EtOAc (150 mL). The combined organic layers were washed with aqueous saturated NaHCO3 (150 mL), brine (150 mL) and then concentrated to a thick syrup. This was dissolved in EtOAc (140 mL) and then treated with hexane (210 mL) and the slurry filtered to afford tert-butyl 4-hydroxy-4-(1,3-thiazol-2-yl)azepane-1-carboxylate as a white solid (68.0 g, 220 mmol) and the material was then subjected to chiral chromatography to afford tert-butyl (4R)-4-hydroxy-4-(1,3-thiazol-2-yl)azepane-1-carboxylate (14.5 g, 48.6 mmol).

Provenance & Evidence