Reaction SMILES: [OH-].[K+:2].[CH3:3][CH:4]([C:10]([O:12]CC)=[O:11])[C:5]([O:7][CH2:8][CH3:9])=[O:6]>C(O)C>[CH3:3][CH:4]([C:10]([O-:12])=[O:11])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[K+:2]
Reactant: CCOC(=O)C(C)C(=O)OCC
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CCOC(=O)C(C)C(=O)[O-]
Temperature: 25 °C
Reaction time: 18 h
Yield: 73.6 %

Procedure:
Potassium ethyl methylmalonate (87 mg) was added to dry tetrahydrofuran (THF; 3 ml) under an argon atmosphere and the suspension cooled to 0° C. A 1.22M solution of n-butyl lithium in n-hexane (0.39 ml) was added over a 10 minute period and the mixture was stirred for 20 minutes. A solution of 4'-bromomethyl- N-(isobutoxycarbonyl)- N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamide (230 mg) dissolved in dry THF (3 ml) was added over a period of 10 minutes. The mixture was allowed to attain ambient temperature and stirring was continued for 1 hour and then it was heated to 50° C. for 30 minutes. The solvent was removed by evaporation and the residue was acidified to pH 2 by the addition of 2M hydrochloric acid. The aqueous phase was extracted with ethyl acetate (3×25 ml) and the combined organic extracts were evaporated to dryness. The residue was purified by chromatography through a Mega Bond Elut column (5 g), eluting first with 10% ethyl acetate in iso-hexane and then 50% ethyl acetate in iso-hexane. Combination of the later fractions containing the required product and evaporation of the solvent gave a gum (51 mg). A portion of this material (20 mg) was suspended in diphenyl ether (0.5 ml) and heated under reflux for 20 minutes. The reaction mixture was diluted with iso-hexane (0.5 ml) and applied to a Mega Bond Elut column (5 g) and eluted with iso-hexane. After removal of all the diphenyl ether, the eluent was changed to ether and the product fractions were collected and combined. The solvent was removed by evaporation and the residue dissolved in ethanol (1.5 ml) containing 5M sodium hydroxide solution (0.04 ml). The mixture was heated under reflux for 2 hours and then cooled. 2M hydrochloric acid (0.1 ml) was added and the solvent was removed by evaporation. The residue was triturated with diethyl ether (10 ml) and filtered. The filtrate was extracted with a saturated aqueous solution of sodium bicarbonate (3×5 ml) and the combined aqueous extracts were acidified to pH2 with 2M HCl. The mixture was extracted with diethyl ether (3×10 ml) and the combined organic extracts were dried (MgSO4) and evaporated to give 4'-(2-carboxypropyl)- N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamide (12.3 mg); 1H NMR (d6 -DMSO): 1.23 (d, 3H), 2.43 (s, 3H), 2.74-2.93 (m, 2H), 3.05-3.25 (m, 1H), 4.0 (s, 3H), 7.32 (br s, 4H), 7.44 (dd, 1H), 7.68-7.85 (m, 2H), 8.24 (dd, 1H); mass spectrum ((positive electrospray (+ve ESP)): 442 (M+H)+. The starting material potassium ethyl methylmalonate was obtained as follows: Potassium hydroxide (6.5 g) was dissolved in absolute ethanol (60 ml) and diethyl methylmalonate (20.3 g) was added in one portion. The reaction mixture was stirred at ambient temperature for 18 hours and heated under reflux for 30 minutes. The solvent was partially removed by evaporating to low volume (~20 ml) and diethyl ether (100 ml) was added. The precipitate which formed was removed by filtration and washed with diethyl ether (2×100 ml) to give potassium ethyl methylmalonate (15.7 g); 1H NMR (d6 -DMSO): 1.10-1.38 (m, 6H), 2.72 (q, 1H), 3.72-4.07 (m, 2H).