Phthalide → o-(Hydroxymethyl)benzamide

Participants

Reaction Conditions

Reaction Steps

A solution of triethylamine (TEA, 0.824 g, 1.13 ml, 8.14 mmol, 1.5 equiv.) in 1,2-dichloroethane (3 ml) was added dropwise under stirring and cooling with ice to a suspension of AlCl3 (0.796 g, 5.97 mmol, 1.1 equiv.) in 1,2-dichloroethane (7 ml). The temperature was maintained at 15-20° C. during the addition and the mixture was then allowed to warm up at room temperature. A solution of 1-dimethoxytrityl-6-amino-hexan-1-ol (16) (2.505 g, 5.97 mmol, 1.1 equiv., prepared as described by Woo and Fung (1996), International Pat. App. Pub. No. WO 96/05215, which is incorporated herein by reference in its entirety) and phthalide (17) (0.728 g, 5.43 mmol, 1.0 equiv.) in 1,2-dichloroethane (3 ml) was added over a period of 20 min and the mixture was stirred at room temperature overnight. The completion of the reaction was confirmed by TLC analysis (EtOAc containing 1% TEA). The reaction mixture was then quenched with an ice-water mixture (30 ml) and stirred for further 30 min. The resulting suspension was filtered through a bed of Celite® and the filter cake was washed with 1,2-dichloroethane (10 ml). The organic phase of the combined filtrates was separated, washed with water (30 ml) and brine (20 ml), dried over MgSO4 and concentrated. The crude product was purified by flash chromatography (15-70% EtOAc in hexanes containing 1% of TEA, gradient elution) yielding 0.80 g (27%) of compound (19) as a pale yellow oil. Rf=0.68 (EtOAc containing 1% TEA). 1H NMR (400 MHz, CD3CN) δ 7.61-7.19 (m, 14H), 6.85 (d, J=8.9 Hz, 4H), 5.33 (s, 1H), 4.50 (s, 2H), 3.75 (s, 6H), 3.32 (q, J=6.6 Hz, 2H), 3.01 (t, J=6.6 Hz, 2H), 1.63-1.53 (m, 4H), 1.44-1.28 (m, 4H).

Provenance & Evidence