Hydrochloric Acid → 2-(3,4-dichloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-acetamide

Participants

Reaction Conditions

Reaction Steps

3.4 g (13.0 mmol) N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-formamide and 4.3 ml (32 mmol) triethylamine are dissolved in 13 ml CH2Cl2. 1.4 g (4.7 mmol) bis(trichloromethyl) carbonate (triphosgene) in 9 ml CH2Cl2 is added at +5° C. The mixture is stirred 4 hours at +5° C. and then cooled to −78° C. A solution of 1.43 ml (13.0 mmol) TiCl4 in 20 ml CH2Cl2 is added and the mixture is stirred for 2 hours at −40° C. 2.5 g (12.9 mmol) 3,4-dichloro-benzaldehyde in 7 ml CH2Cl2 is added dropwise and the mixture stirred for 17 hours at +20° C. The mixture is hydrolysed with 7 ml HCl 5N, stirred 30 minutes at +20° C. and washed with water. After evaporation the residue is submitted to flash-chromatography (ethyl acetate 6, hexanes 4) to give 2.7 g (48%) of the 2-(3,4-dichloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-acetamide. 1H-NMR (300 MHz, CDCl3): 1.15 (t, 3 H, CH2CH3), 2.22 (m, 2 H, CH2CH3), 2.75 (t, 2 H, CH2CH2), 3.51 (m, 2 H, CH2CH2), 3.69 (d, 2 H, OH), 3.83 (s, 3 H, OCH3), 4.74 (m, 2 H, OCH2), 4.96 (d, 1 H, CHOH), 6.27 (t, 1 H, NH), 6.58 (m, 1 H), 6.68 (m, 1 H), 6.92 (d, 1 H), 7.19 (d, 1 H), 7.42 (d, 1 H) and 7.49 (m, 1 H, CH arom.).

Provenance & Evidence