Ethyl Bromide → Methyl 4-ethoxy-3-formylbenzoate

Participants

Reaction Conditions

Reaction Steps

A suspension of methyl 3-formyl-4-hydroxy-benzoate (3.0 g, 16.7 mmol), bromoethane (2.7 g, 1.85 mL, 24.9 mmol) and powdered K2CO3 (6.9 g, 49.9 mmol) in DMF (15 mL) was heated at 40° C. for 16 hours. After 16 hours, a further aliquot of bromoethane (1 mL) was added and the reaction mixture was heated for a further 2 hours. The reaction mixture was diluted with DCM (50 mL), filtered and concentrated in vacuo to give a yellow solid, which was diluted with ether (200 mL), washed sequentially with water (50 mL), sat. aq. NaHCO3 (50 mL) and brine solution (50 mL). The organics were separated, dried over MgSO4 and concentrated in vacuo to give methyl 4-ethoxy-3-formylbenzoate (3.52 g, 100%) as a white solid. ESI-MS m/z calc. 208.0. Found 209.3 (M+1)+; Retention time: 1.34 minutes (3 min run). Methyl 4-ethoxy-3-formylbenzoate (1.73 g, 8.91 mmol) was dissolved in THF (20 mL) and cooled to 0° C. LiBH4 (100 mg, 4.59 mmol) was added and the reaction mixture was stirred for 1 hour, then slowly quenched with dropwise addition of acetic acid. The reaction mixture was concentrated in vacuo, diluted with ethyl acetate (50 mL), washed sequentially with sat. aq. NaHCO3 (20 mL) and brine (20 mL). The organics were separated, dried over MgSO4 and purified by silica gel column chromatography using 0-100% EtOAc/DCM as eluent to give methyl 4-ethoxy-3-(hydroxymethyl)benzoate (1.6 g, 46%) as a white solid. ESI-MS m/z calc. 210.0. Found 211.3 (M+1)+; Retention time: 1.11 minutes (3 min run); 1H NMR (400 MHz, CDCl3) δ 8.05-7.86 (m, 2H), 6.99-6.79 (m, 1H), 4.72 (s, 2H), 4.16 (q, J=7.0 Hz, 2H), 3.89 (s, 3H), 1.64 (d, J=7.0 Hz, 2H), 1.47 (t, J=7.0 Hz, 3H).

Provenance & Evidence