Acetic Acid → HCID 23626788, compound

HRID 1375573Notes

Reaction equation

[C:1]([O:9][C:10]1[C:11]([C:34]([O:36][CH3:37])=[O:35])=[N:12][C:13]([C@@H:17]2[CH2:21][C:20]([F:23])([F:22])[CH2:19][N:18]2[C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])=[N:14][C:15]=1[OH:16])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Li+].S(OC)(O[CH3:44])(=O)=O.C(O)(=O)C>O1CCOCC1.C(OCC)(=O)C.O>[CH3:37][O:36][C:34]([C:11]1[N:12]=[C:13]([C@@H:17]2[CH2:21][C:20]([F:23])([F:22])[CH2:19][N:18]2[C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[N:14]([CH3:44])[C:15](=[O:16])[C:10]=1[O:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:35]

Participants

Conditions

Temperature: 38 °C

Procedure

Methyl 5-(benzoyloxy)-2-{(2S)-1-[(benzyloxy)carbonyl]-4,4-difluoropyrrolidin-2-yl}-6-hydroxypyrimidine-4-carboxylate dissolved in dry 1,4-dioxane was added to a suspension of LiH (1.4 eq.) in dioxane. The mixture was stirred at 38° C. for 45 minutes and then cooled down to room temperature. Dimethyl sulphate (1.3 eq.) was added and the mixture was warmed to 58° C. for 1 hour. The reaction mixture was cooled down to 16° C. and glacial acetic acid (0.1 eq) was added, followed by water and ethyl acetate. The combined organic layers were dried (Na2SO4), filtered and concentrated to an oil which was cromatographed through silica gel (eluent: ethyl acetate:petroleum ether=3:7) to give the desired compound as a 1:1 mixture of two rotamers by 1H NMR

Workup

temperaturecooled down to room temperature
temperaturethe mixture was warmed to 58° C. for 1 hour
temperatureThe reaction mixture was cooled down to 16° C.
dry with materialThe combined organic layers were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated to an oil which

Sources & evidence

ORD record: ord-bf3b7e16f1964693b1a1fd29d7705042
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07169780B2

Reaction notes

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