N-(2-fluoroethyl)aniline → 9-(2-fluoro-ethyl)-2-methyl-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-bromo-2-hydroxy-5-methyl-cyclohex-1-enecarboxylic acid diethylamide (47; prepared according to Example 11(d)) (2.0 g, 7 mmol) and (2-fluoro-ethyl)-phenyl-amine (24; prepared according to Example 4(a)) (1.9 g, 14 mmol) was stirred under N2 at 50° C. for 3 h and the reaction turned brown. The resulting mixture was dissolved in propan-2-ol (7 mL) and dry zinc chloride (2.86 g, 21 mmol) was added. The mixture was heated to reflux under N2 for 16 h and then concentrated in vacuo. The residue was dissolved in ethyl acetate (100 mL) and washed with 2 N HCl (30 mL), water (2×30 mL) and aqueous potassium carbonate solution (2×30 mL) then dried and concentrated in vacuo. The crude mixture was purified by SCX cartridge (40 mL) and then silica gel chromatography eluting with petrol (A) and ethyl acetate (B) (0-100% B, 100 g, 12 CV, 85 mL/min) to afford 400 mg (17%) of 9-(2-fluoro-ethyl)-2-methyl-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide (non-radioactive imaging agent as a white solid. The structure was confirmed by 1H NMR (300 MHz, CDCl3) δH 1.10-1.35 (9H, m, CH3 and N(CH2CH3)2), 1.95-2.10 (2H, m, 3-CH2), 2.30-2.50 (1H, m, 2-CH), 2.70-2.80 (2H, m, 1-CH2), 3.40-3.70 (4H, m, N(CH2CH3)2), 4.05-4.15 (1H, m, 4-CH), 4.30 (2H, dm, J=21 Hz, NCH2CH2F), 4.65 (2H, dm, J=41 Hz, NCH2CH2F), and 7.00-7.30 (4H, m, NCCHCHCHCH.

Provenance & Evidence