Acetic Acid → HCID 23626788, compound

HRID 2114800Notes

Reaction equation

HRID 2114800 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

8

Reactant 4

HCID 176Acetic AcidHCID 6497Dimethyl SulfateHCID 62714Lithium hydrideHCID 178499095HCID 178499095, compound

Product 1

HCID 23626788HCID 23626788, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

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 chromatographed 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

  1. temperaturecooled down to room temperature
  2. temperaturethe mixture was warmed to 58° C. for 1 hour
  3. temperatureThe reaction mixture was cooled down to 16° C.
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to an oil which
  7. customwas chromatographed through silica gel (eluent: ethyl acetate:petroleum ether=3:7)

Sources & evidence

ORD record
ord-4795fa91a5c348368d70c428285bdf17
Source dataset
uspto-grants-2008_10
Patent number
US07435734B2

Reaction notes

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