7-CHLORO-2-METHYLQUINOLINE-3-CARBOXYLIC ACID synthesis

Yield:171270-39-6 10%

Reaction Conditions:

Stage #1: ethyl 7-chloro-2-methylquinoline-3-carboxylatewith water;lithium hydroxide in tetrahydrofuran at 50;
Stage #2: with hydrogenchloride in water; pH=7;

Steps:

23.23A

Example 237-CHLORO-2-METHYL-QUINOLINE-3-CARBOXYLIC ACID [(R)-1-(4-METHANESULFONYL-AMINO-3-METHYLPHENYL)ETHYL]AMIDE 23A) 7-CHLORO-2METHYLQUINOLINE-3-CARBOXYLIC ACID To a stirred solution of 7-chloro-2-methylquinoline-3-carboxylic acid ethyl ester (1.0 g, 4 mmol) in tetrahydrofuran (36 mL) and ethanol (12mL) was added a solution of lithium hydroxide (287 mg) in water (12 mL). The reaction was stirred at 50° C. overnight. After cooling, the organic solvents were evaporated and the aqueous solution was acidified to pH 7.0 with 2N HCl. The product was then extracted into EtOAc (2×100 ml) and the combined organics were washed with brine (100 ml), dried (MgSO₄), filtered and concentrated. Trituration with DCM/hexanes gave the title compound (100 mg, 10%) as an off-white solid.¹H NMR (400 MHz, DMSO-d₆) δ 2.86 (s, 3H), 7.64 (d, 1H, J=7.4 Hz), 8.01 (s, 1H), 8.13 (d, 1H, J=8.7 Hz), 8.82 (s, 1H).LC/MS: 220 m/z (M-H)^-; r.t.=2.10 min

References:

US2012/88746,2012,A1 Location in patent:Page/Page column 51