Chloride → Fenretinide

Participants

Reaction Steps

A mixture of all-trans retinoic acid (ATRA) (200 mg, 0.66 mmol) in dry DMF (2 mL) and dry CH2Cl2 (2 mL) was stirred under nitrogen atmosphere for 1 h. Oxalyl chloride (2.5 mmol, 215 μL) was added drop by drop at 0° C. The deep red reaction mixture was stirred for another 1.5 h at room temperature under nitrogen atmosphere. Very carefully removed the solvent, then added dry DMF (2 mL) for immediate use. At 0° C. under nitrogen atmosphere, Retinoyl chloride solution was added dropwise to a solution of 4-aminophenol (1.331 mmol, 145.3 mg) and triethylamine (1.997 mmol, 280 μL) in dry DMF (2 mL). The dark-colored reaction mixture was stirred at room temperature until TLC analysis indicated none remaining (about 2˜3 h). The reaction was quenched with saturated NH4Cl and extracted with ethyl acetate. The extracts were washed with H2O and brine, then dried overage Na2SO4, and evaporated. The residue was purified by flash column chromatography using hexane/ethyl acetate (3/1) as the eluent to give 4-HPR as a yellow solid. 1H-NMR(300 MHz, CDCl3): δ7.42 (d, 2H), 7.11 (s, 1H), 6.99 (dd, 1H), 6.83 (d, 2H), 6.33˜6.18 (m, 4H), 5.80 (s, 1H), 2.44 (s, 3H), 2.04 (br s, 5H), 1.74 (s, 3H), 1.64˜1.62 (m, 2H), 1.33 (m, 2H), 1.05 (s, 6H).

Provenance & Evidence