Acetic Acid → HCID 23626787, compound

HRID 1161923Notes

Reaction equation

HRID 1161923 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([O:11][C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:9]([OH:20])[N:8]=[C:7]([C@@H:21]2[CH2:25][C@H:24]([F:26])[CH2:23][N:22]2[C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:28])[N:6]=1)=[O:4].[H-].[Li+].S(OC)(O[CH3:43])(=O)=O.C(O)(=O)C>O1CCOCC1.C(OCC)(=O)C.O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([C@@H:21]2[CH2:25][C@H:24]([F:26])[CH2:23][N:22]2[C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:28])[N:8]([CH3:43])[C:9](=[O:20])[C:10]=1[O:11][C:12](=[O:19])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:4]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 6497Dimethyl SulfateHCID 62714Lithium hydrideHCID 178499097HCID 178499097, compound

Product 1

HCID 23626787HCID 23626787, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
38 °C

Procedure

Methyl-5-(benzoyloxy)-2-{(2S,4S)-1-[(benzyloxy)carbonyl]-4-fluoropyrrolidin-2-yl}-6-hydroxypyrimidine-4-carboxylate, dissolved in dry dioxane, was added to a suspension of lithium hydride (1.2 eq.) in dry dioxane. The reaction mixture was stirred at 38° C. for 45 minutes and then cooled down to room temperature. Dimethyl sulfate (1.3 eq.) was added and the mixture was heated to 58° C. and stirred at this temperature for 3 hours. The reaction mixture was then cooled down and glacial acetic acid (0.2 eq.) was added, followed by water and ethyl acetate. The aqueous layer was separated and extracted with ethyl acetate; the organic phase was dried over Na2SO4 and filtered to give, after concentration, a crude that was purified by flash chromatography (eluent petroleum ether: ethyl acetate from 4:6 to 2:8) to give the title compound as a 4.6:5.4 mixture of rotamers by NMR.

Workup

  1. temperaturecooled down to room temperature
  2. temperaturethe mixture was heated to 58° C.
  3. stirringstirred at this temperature for 3 hours
  4. temperatureThe reaction mixture was then cooled down
  5. customThe aqueous layer was separated
  6. extractionextracted with ethyl acetate
  7. dry with materialthe organic phase was dried over Na2SO4
  8. filtrationfiltered
  9. customto give
  10. concentrationafter concentration
  11. customa crude that was purified by flash chromatography (eluent petroleum ether: ethyl acetate from 4:6 to 2:8)

Sources & evidence

ORD record
ord-f26f3ce993aa43cb9fd253a470b160be
Source dataset
uspto-grants-2010_10
Patent number
US07820660B2

Reaction notes

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