Methanol → Racemic methyl 5-hydroxy-5-(thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To an oven-dried, N2-purged flask was added isopropyl magnesium chloride lithium chloride complex (7.91 mL, 10.3 mmol) and THF (18.4 mL) and the solution was cooled to 0° C. A solution of thiazole (0.813 g, 9.55 mmol) in THF (9.18 mL) was then added, and the reaction was stirred for 45 min at 0° C., and then cooled to −10° C. A solution of methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylate (1.5 g, 7.34 mmol) in THF (9.18 mL) was then added, after which the reaction was allowed to warm to rt over a period of 4 h. MeOH (5 mL) was then added and the reaction was partitioned between water (50 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (2×50 mL), then the combined organic phases were dried (MgSO4), filtered and concentrated. The product was purified by silica gel chromatography using a gradient solvent system of 0-70% EtOAc/DCM. The product-containing fractions were collected and concentrated to give racemic methyl 5-hydroxy-5-(thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carboxylate as a yellow oil. The enantiomers were resolved by chiral SFC using a Chiral Technology AY-H 2.1×25 cm, 5 uM column, eluting with 20%-50% MeOH+0.25% dimethyl ethylamine/CO2. At a flow rate of 70 mL/min, the two enantiomers eluted at 2.38 min and 2.79 min.

Provenance & Evidence