alpha-Bromo-o-fluorotoluene → HCID 52951670, compound

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Reaction Steps

To a stirred solution of tert-butyl 3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)propanoate (4.9 g, 13.78 mmol) in tetrahydrofuran (41 mL) under N2 and cooled to −78° C., lithium bis(trimethylsilyl)amide 1M (41.35 mL, 41.45 mmol) is added dropwise. The resulting mixture is stirred at that temperature for 3 hours. Then, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.33 mL, 11.03 mmol) is added, and the resulting solution is stirred at the same temperature for 30 min. To the resulting mixture, 2-fluorobenzyl bromide (2.33 mL, 19.3 mmol) in dry tetrahydrofuran (1 mL) is added and stirring is continued. The temperature is allowed to go from −78° C. to room temperature overnight. The crude reaction mixture is quenched with aqueous saturated solution of ammonium chloride and extracted with ethyl acetate. The organic layer is decanted, dried over magnesium sulfate, the solvent is evaporated and the crude obtained is purified by normal phase Isco chromatography using ethyl acetate/hexane from 5/95 to 20/80 to yield 5.06 g of the title compound obtained as colorless oil. MS (m/z): 464 (M+1).

Provenance & Evidence