Cesium carbonate → Ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6-chlorochroman-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 4-iodobenzoate (25.9 g, 85.2 mmol) and 2,2,6,6-tetramethyl-3,5-heptanedione (7.01 mL, 34.1 mmol) were diluted with NMP (70 mL) and bubbled with Argon for 20 minutes. Copper (I) chloride (16.9 g, 170 mmol), ethyl 6-chloro-7-hydroxychroman-4-carboxylate (24.0 g, 93.7 mmol) and cesium carbonate (55.5 g, 170 mmol) were combined and added to the reaction using a small funnel which was rinsed with NMP (30 mL). The reaction was purged for an additional 10 minutes and then heated to 100° C. and stirred for 5 hours under Argon. The reaction was cooled and loaded directly onto a silica plug (2 kg) and eluted with 10% ethyl acetate/hexanes to yield 10 g of crude product. The crude material was purified by silica gel column chromatography, eluting with 5% ethyl acetate/hexanes to 50% ethyl acetate/hexanes to provide the desired product (14 g, 32.3 mmol, 38.0% yield) as a viscous oil.

Provenance & Evidence