2-Bromo-3-methoxypropanoic acid

The solution of In a dry equipment under nitrogen, 2, 3-dibromo ethyl propionate (VII) available commercially (1 equiv) is dissolved in 4 volumes of dry methanol and the solution is cooled to -10 0C under stirring. A 25% w/w solution of sodium methoxide in methanol (1.1 equiv) is slowly added such as the temperature is maintained below -5 0C. After addition, the mixture is allowed to warm to room temperature and the reaction is post-stirred at 20 0C for 1 hour.20 % aqueous sodium hydroxide (1 equiv) is added slowly at a temperature maintained below 23 0C. The reaction mixture is then stirred at 20 0C for 1 hour.37% aqueous HCI is slowly added till pH 5-6 and the reaction mixture concentrated to the minimal agitation volume, i.e. 1 volume vs compound (VII), under vacuum at a temperature of maximum 40 0C.37% aqueous HCI is added until the pH is 2 and the salty residue is taken in a minimum amount of water (~0.6 volumes) to get a solution and the compound (VId) is extracted with isobutylacetate (3 X 2 volumes). The organic layer is evaporated to ca. 4 volumes affording a solution of Methyl 2-bromo-3-methoxypropionate (L. OOG) in tetrahydrofuran (8ml) was stirred at 10C and lithium hydroxide monohydrate (0.21g) in water (1. 5ML) was added dropwise. On complete addition, the mixture was stirred for 1.5 hours, the colourless solution was evaporated under reduced pressure to a small volume then the aqueous solution was taken to pH 3 with dilute sulphuric acid. The mixture was extracted with diethyl ether (SOML) and the organic phase separated, washed with brine, dried over magnesium sulphate then evaporated under reduced pressure to give the required product (0.6g) as a colourless liquid. IH NMR (CDC13) 8 : 3.45 (3H, s); 3.78 (1H, M) ; 3.92 (1H, M) ; 4.38 (1H, M) ; 6.65 (1H, br s).EXAMPLE 3 This Example illustrates the preparation OF 2-(3-CYANO-5-METHOXYPHENOXY)-N-(2- methylpent-3-yn-2-yl) -3-methoxypropionamide (Compound No. 16 in Table 1) Stage 1: Preparation OF 2-BROMO-N-(4-METHYLPENT-2-AN-4-YL) 3-METHOXYPROPIONAMIDE. Step 1: Preparation of Methyl 2-bromo-3-methoxypropionate (l.OOg) in tetrahydrofuran (8ml) was stirred at10C and lithium hydroxide monohydrate (0.21g) in water (1.5ml) was added dropwise.On complete addition, the mixture was stirred for 1.5 hours. The colourless solution wasevaporated under reduced pressure to a small volume and the aqueous solution was takento pH 3 with dilute sulphuric acid. The mixture was extracted with diethyl ether (50ml)and the organic phase separated, washed with brine, dried over magnesium sulphate thenevaporated under reduced pressure to give the required product (0.6g) as a colourlessliquid.'H NMR (CDC13) 5: 3.45(3H, s); 3.78(1H, m); 3.92(1H, m); 4.38(1H, m); 6.65(1H, bs).2-Bromo-3-methoxypropionic acid (0.366g) was dissolved in dry dichloro- methane (4ml) containing dry N, N-DIMETHYLFORMAMIDE (0. 05ML) with stirring and oxalyl chloride (0.254g) was added. The mixture was stirred at ambient temperature for 2 hours then evaporated under reduced pressure to give 2-Bromo-3-methoxypropionic acid (0. 51g) was dissolved in dry dichloromethane (LOML) containing DRYN, N-DIMETHYLFORMAMIDE (0. 05ML) with stirring and oxalyl chloride (0.36g) was added. The mixture was stirred at ambient temperature for 2 hours then evaporated under reduced pressure to give STEP 2: PREPARATION OF 2-BROMO-N-(4-METHYLPENT-2-YN-4-YL) 3-METHOXYPROPIONAMIDE. 2-BROMO-3-METHOXYPROPIONIC acid (0.366g) was dissolved in dry dichloro- methane (4ML) containing dry N, N-DIMETHYLFORMAMIDE (0. 05ML) with stirring and oxalyl chloride (0.254g) was added. The mixture was stirred at ambient temperature for 2 hours then evaporated under reduced pressure to give 2-BROMO-3-METHOXYPROPIONIC acid chloride (C=O, v 1780CMS~1). The acid chloride was dissolved in dry dichloromethane (6ML) and 4-amino-4-methylpent-2-yne hydrochloride (0.267g) was added. The mixture was cooled to 3C and triethylamine (0.404g) was added dropwise, while keeping the reaction temperature between 0-5C. The suspension that had formed was stirred at ambient temperature for 1 hour, diluted with further dichloromethane and washed with hydrochloric acid (2M). The organic phase was separated, dried over magnesium sulfate and evaporated under reduced pressure to give a gum. The gum was fractionated by chromatography (silica: hexane/ethyl acetate, 3: 2 by volume) to give the required product (0.300g) as a colourless SOLID.'H NMR (CDC13) 8 : 1. 63 (6H, s); 1.82 (3H, s); 3.44 (3H, s); 3.88 (2H, M) ; 4.32 (1H, m); 6.62 (1H, s).2-Bromo-3-methoxypropionic acid (Q.366g) was dissolved in dry dichloro-methane (4ml) containing dry TV, W-dimethylformamide (0.05ml) with stirring and oxalylchloride (0.254g)' was added. The mixture was stirred at ambient temperature for 2 hoursthen evaporated under reduced pressure to give

Molecular Weight:183.00
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:181.95786
Monoisotopic Mass:181.95786
Topological Polar Surface Area:46.5
Heavy Atom Count:8
Complexity:83.4
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes