Acetic Acid → 4-((4-Bromo-5-chlorothiophen-2-yl)methyl)morpholine

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Reaction Steps

Morpholine (15.2 mL), acetic acid (9.1 mL), and then sodium triacetoxy-borohydride (50.3 g) is added to a solution of 4-bromo-5-chloro-2-thiophene-carbaldehyde (Preparation 16, 35.7 g) in 1,2-dichloroethane (600 mL) at 0° C. The mixture is allowed to warm to room temperature, and after 18 h, it is quenched with a 2N NaOH solution (200 mL) with ice bath cooling. The organic layer is separated and washed with a 1N NaOH solution (2×200 mL). The combined aqueous layers are extracted with CH2Cl2 (2×100 mL). The combined organic layers are extracted with 0.25 M HCl solution (4×500 mL) and the resulting aqueous layer is made basic with 2N NaOH solution. The mixture is then extracted with CH2Cl2 (4×500 mL) and the organic layer is dried (Na2SO4) and concentrated to afford 39.24 g of the title compound as a light yellow oil. Physical characteristics. 1H NMR (400 MHz, DMSO-d6) δ 7.03, 3.63, 3.57, 2.42; 3C NMR (100 MHz, CDCl3) δ 140.9, 127.3, 125.9, 109.2, 66.9, 57.6, 53.3; MS (ESI+) m/z 296 (M+H)+. Anal. Found: C, 36.49; H, 3.77; N, 4.70; Br, 26.73; Cl, 12.06; S, 10.72.

Provenance & Evidence