Hydrochloric Acid → [(3-{[5-(4-Ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidin-4-yl]oxy}cyclohexyl)oxy]acetic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

1.4 ml of an 11.25N sodium hydroxide solution is added at 70° C. to a solution of 700 mg (1.62 mmol) of 3-{[5-(4-ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidin-4-yl]oxy}cyclohexanol in 15 ml of toluene. After adding 55 mg (0.16 mmol) of tetra-n-butylammonium hydrogensulphate and 631 mg (3.24 mmol) of bromoacetic acid tert-butyl ester, stir the reaction mixture at 70° C. for 30 hours. Then add a further 330 mg (1.69 mmol) of bromoacetic acid tert-butyl ester to the reaction mixture and stir at 70° C. for another 14 hours. After cooling to room temperature, adjust to pH 7 with conc. hydrochloric acid. Extract with dichloromethane. Wash the organic phase with satd. sodium chloride solution, dry over sodium sulphate, filter and concentrate under reduced pressure. Purify the residue by means of preparative RP-HPLC (eluent:water/acetonitrile gradient). 632 mg (69% of theory) of the desired product are obtained as a racemic diastereomer mixture.

Provenance & Evidence