2-Chlorobenzaldehyde → HCID 10595300, compound

Participants

Reaction Steps

(2-Bromophenyl)[2-chloro-4-(2-carboxy-E-ethenyl)phenyl]sulfide was prepared by the procedures described in Example 1 substituting 2,4 dichlorothiophenol with 2-bromothiophenol, 2-chlorobenzaldehyde with 3,4 dichlorobenzaldehyde. 1-(3-aminopropyl)-5-((S)-thexyldimethylsilyloxymethyl)-2-pyrrolidinone (0.2818 g, 0.8959 mmol) was added to a solution of this cinnamic acid (0.3312 g, 0.8959 mmol), 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.3435 g, 1.79 mmol), and 1-hydroxybenzotriazole hydrate (0.1816 g, 1.34 mmol) in DMF (4.0 mL). After stirring for 12 hours the reaction mixture was diluted with EtOAc (250 mL), extracted with sat. NH4Cl (1×75 mL), extracted with H2O (2×75 mL), rinsed with brine (75 mL), and dried over Na2SO4. The resultant thexyldimethylsilyl alcohol was purified by flash chromatography (EtOAc) on silica gel (0.4974 g, 83%). Tetrabutylammonium fluoride (0.68 mL of 1.0 M solution in THF) was added dropwise to a solution of this protected alcohol (0.4544 g, 0.682 mmol) in THF (1.7 mL). After 2 hours the reaction was diluted with EtOAc (50 mL) and extracted with sat. NH4Cl (1×25 mL), extracted with H2O (2×25 mL), rinsed with brine (25 mL), and dried over Na2SO4. Flash chromatography (EtOAc →9:1 CH2Cl2:MeOH) on silica gel yielded the title compound (0.3144 g, 88%). 1H-NMR (DMSO-d6, 300 MHz) δ 8.14 (t, J=5.5 Hz, 1H), 7.81 (m, 2H), 7.53 (dd, J=8.3, 1.7 Hz, 1H), 7.44 (dt, J=7.7, 1.5, 1H), 7.40 (dt, J=7.7, 1.8, 1H), 7.39 (d, J=15.6 Hz, 1H), 7.28 (dd, J=7.7, 1.8 Hz, 1H), 7.05 (d, J=8.1 Hz, 1H), 6.67 (d, J=15.6 Hz, 1H), 4.84 (t, J=5.1 Hz, 1H), 2.94-3.62 (m, 8H), 1.54-2.29 (m, 6H), MS(APCI) (M+H)+ at m/z 523, 525, 527, 529.

Provenance & Evidence