Toluene → Methyl (2s)-2-ethyl-2,3-dihydro-1-benzofuran-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of the acid from step 1 (4.0 g, ca. 20 mmol) in 1:4 DMF:toluene (100 mL.) was added 60% NaH in mineral oil (1.76 g, 44 mmol) in 3 portions. The reaction mixture was stirred at 110° C. under N2 for 4 hrs. The reaction was cooled to room temperature and poured into cold water (100 mL). The aqueous layer was washed with hexane (50 mL), acidified with 2 N aqueous HCl and extracted with ethyl acetate (3×50 mL). The extracts were washed with brine (50 mL), dried and concentrated. The residue was dissolved in 7:1 benzene:MeOH (80 mL) and treated with TMSCHN2 (1M in hexane) until gas evolution ceased. The reaction was concentrated and the residue was chromatographed on silica gel eluting with 85:15 hexane:ethylacetate to give methyl (2S)-2-ethyl-2,3-dihydro-benzofuran-2-carboxylate.

Provenance & Evidence