Potassium Hydroxide → Darusentan, (+/-)-

HRID 2214793Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([O:11][CH:12]([C:17]([O:30][CH3:31])([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:13]([O:15]C)=[O:14])[N:4]=1.[OH-].[K+]>O1CCOCC1.O>[CH3:10][O:9][C:7]1[CH:8]=[C:3]([O:2][CH3:1])[N:4]=[C:5]([O:11][CH:12]([C:17]([O:30][CH3:31])([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:13]([OH:15])=[O:14])[N:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

2.12 g (5 mmol) of methyl 2-(4,6-dimethoxy-pyrimidin-2-yl-oxy)-3-methoxy-3,3-diphenylpropionate were dissolved in 50 ml of dioxane, 10 ml of 1 N KOH solution were added, and the mixture was stirred at 100° C. for 3 h. The solution was diluted with 300 ml of water and extracted with ethyl acetate to remove unreacted ester. The aqueous phase was then adjusted to pH 1–2 with dilute hydrochloric acid and extracted with ethyl acetate. After drying over magnesium sulfate and removal of the solvent by distillation, the residue was mixed with an ether/hexane mixture, and the precipitate which formed was filtered off with suction. After drying, 1.85 g (90%) of a white powder remained.

Workup

extractionextracted with ethyl acetate
customto remove unreacted ester
extractionextracted with ethyl acetate
dry with materialAfter drying over magnesium sulfate and removal of the solvent by distillation
additionthe residue was mixed with an ether/hexane mixture
customthe precipitate which formed
filtrationwas filtered off with suction
customAfter drying

Sources & evidence

ORD record: ord-64791a293113421e954f521deb862208
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07109205B2

Reaction notes

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