4-Fluorophenylhydrazine hydrochloride → 6-O-tert-butyl 4a-O-methyl 1-(4-fluorophenyl)-4,5,7,8-tetrahydropyrazolo(3,4-g)isoquinoline-4a,6-dicarboxylate

Participants

Reaction Steps

A mixture of (R)-7-[1-hydroxymeth-(Z)-ylidene]-6-oxo-4,6,7,8-tetrahydro-3H-isoquinoline-2,8a-dicarboxylic acid 2-tert-butyl ester 8a-methyl ester (3.8 g), 4-fluorophenylhydrazine hydrochloride (2.7 g), sodium acetate (1.4 g) and acetic acid (30 mL) was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure, and the residue was partitioned between diethyl ether and 2.0 M aqueous hydrochloric acid solution. The organic phase was washed with water, aqueous potassium carbonate solution and brine, and then dried over sodium sulfate. The solvent was removed under reduced pressure, and the residue was triturated with a mixture of cyclohexane and diethyl ether to afford the title compound as a yellow solid (3.7 g). 1H NMR (CDCl3): δ 7.48-7.39 (m, 3H), 7.21-7.12 (m, 2H), 6.45-6.41 (s, 1H), 4.69-4.55 (d, 1H, J=13 Hz), 4.32-3.98 (m, 1H), 3.64 (s, 3H), 3.51-3.33 (m, 1H), 3.00-2.71 (m, 3H), 2.59-2.51 (d, 1H, J=16 Hz), 2.48-2.34 (m, 1H), 1.46 (s, 9H).

Provenance & Evidence