Pyridine → HCID 57436801, compound

Participants

Reaction Steps

1,2,3,4-tetrahydroquinolin-2-carboxylic acid ethyl ester (25 mmol) in THF (5 ml/mol) was added dropwise at 0° C. to a suspension of LAH (2 eq.) in THF (50 ml). The reaction mixture was stirred for 1 h at RT and then heated under reflux for 4 h. After addition of aqueous saturated Na2SO4 solution, filtration was carried out and the organic solvent was removed in vacuo. The product was purified by column chromatography (3:7 ethyl acetate/hexane). Yield: 50%. 2. Pyridine (5 eq.), DMAP (0.5 eq.) and 3,4-dichlorobenzenesulfonyl chloride (1.2 eq.) dissolved in CH2Cl2 (50 ml) were added to a suspension, cooled to 0° C., of the alcohol (16 mmol) in CH2Cl2 (5 ml/mmol). After stirring for 5 h at 0° C., CH2Cl2 was added and the mixture was washed with aqueous copper sulfate solution, water and saturated NaCl solution. After drying over sodium sulfate and filtration, the solvent was removed in vacuo. The product was purified by column chromatography (5:95 ethyl acetate/CH2Cl2). Yield: 80%. 3. A solution of the sulfonamide (16 mmol) dissolved in THF (100 ml) was added dropwise, with stirring, to a suspension, cooled to 0° C., of NaH (2 eq.) in THF (300 ml). After stirring for 45 min. at that temperature, a solution of bromoacetic acid tent-butyl ester (1.5 eq.) in THF (50 ml) was added. The reaction mixture was heated for 20 h at 50° C. It was then cooled to 0° C., ice was added, and extraction with ethyl acetate was carried out. The organic phase was washed with aqueous saturated NaCl solution and dried over Na2SO4. After filtration, the solvent was removed in vacuo. The product was purified by column chromatography (1:9 ethyl acetate/hexane). Yield: 50%. 4. TFA (13 eq.) was added at a temperature of 0° C., with stirring, to a solution of the tert-butyl ester (1 eq.) in CH2Cl2 (10 ml/mmol). After stirring for 3 h at 0° C., the solvent was removed in vacuo. The crude product was used without being worked up further.

Provenance & Evidence