Potassium Hydroxide → Darusentan, (+/-)-

HRID 1801619Notes

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 1N 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. Melting point 167° C.

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-bef143caa4d64c7b9163ca355525ca6a
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349843B2

Reaction notes

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