2-Hydroxy-3-methoxy-3,3-diphenylpropionic acid methyl ester

5 g (19.6 mmol) of methyl 3, 3-diphenyl-2, 3-epoxypropionate, Was dissolved in 50 ml of anhydrous methanol, 0.1 ml of boron trifluoride etherate was added at 0 ° C.The mixture was stirred at 0 ° C. for 2 hours, The mixture was further stirred at room temperature for 12 hours.The solvent was distilled off, The residue was placed in ethyl acetate, Washed with sodium bicarbonate and water, And dried over magnesium sulfate.After removing the solvent by distillation, 5.5 g (88percent) of a pale yellow oil remained.500 g (2.74 mol) of benzophenone was dissolved in 1200 mL of toluene. After purging with nitrogen, 267 g (4.94 mol) of sodium methoxide was added and the suspension was stirred. The suspension was cooled and a solution of 410 mL (4.68 mol) of methyl chloroacetate in toluene (300 mL) was slowly added dropwise over 90 minutes while maintaining the temperature at -8 to 4 ° C., and then the solution was cooled to -3 to 4 ° C. For 1 hour. After adding 1000 mL of water and stirring for 15 minutes, the organic layer obtained by liquid-liquid separation was washed with 1000 mL of water. The solvent was distilled off under reduced pressure, and the obtained residue (methyl (RS) -3, 3-diphenyl-2, 3-epoxypropenoate) was dissolved in 1200 mL of methanol and cooled at 0 ° C. to obtain p- A solution of 15 g (0.08 mol) of toluenesulfonic acid monohydrate in methanol (150 mL) was slowly added dropwise over 30 minutes. The mixture was stirred at 0 ° C. for 1.5 hours, and the precipitated crystals were collected by filtration. The obtained crystals were dissolved in 2500 mL of ethyl acetate and washed twice with 1000 mL of 5percent sodium carbonate aqueous solution. The solvent was distilled off under reduced pressure, 1000 mL of hexane was added to the obtained residue, suspended and stirred at room temperature for 1.5 hours, and then stirred at 0 ° C. for 1 hour. The crystals were collected by filtration and dried under reduced pressure at 60 ° C. for 5 hours to obtain 659 g (yield: 84percent) of methyl (RS) -2-hydroxy-3-methoxy-3, 3-diphenylpropanoate.Step-II : preparation of methyl- 2-hydroxy-3-methoxy-3, 3-diphenyl propionate (III) :Into a 5L round bottomed flask a mixture of methanol(1.2L) and compound of formula - I (660g) from the previous step were charged and stirred for 15 minutes. p-Toluene sulphonic acid(15g dissolved in 150ml methanol) was slowly added during 30 minutes at 25-55°C. The reaction mass was brought to room temperature, maintained at the same temperature for 2hours was filtered and the filtered compound was dissolved in ethyl acetate(3L). Ethyl acetate layer was washed with 5percent sodium bicarbonate solution(2xlL). Ethyl acetate layer was distilled off completely under vacuum. To the residue hexane(l L) was charged and maintained under stirring for 2hours. The product was filtered and dried at 50-60°C Dry weight : 560g (75percent)Purity by HPLC : 99.9percentMelting range : 100-102°C

Ambrisentan intermediate.

Molecular Weight:286.32
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:6
Exact Mass:286.12050905
Monoisotopic Mass:286.12050905
Topological Polar Surface Area:55.8
Heavy Atom Count:21
Complexity:312
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes