Hydrochloric Acid → HCID 21098180, compound

HRID 1161926Notes

Reaction equation

HRID 1161926 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@@H:20]([O:22][CH3:23])[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.Cl>O1CCOCC1>[CH3:37][O:36][C:34]([C:11]1[N:12]=[C:13]([C@@H:17]2[CH2:21][C@@H:20]([O:22][CH3:23])[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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6497Dimethyl SulfateHCID 62714Lithium hydrideHCID 178499098HCID 178499098, compound

Product 1

HCID 21098180HCID 21098180, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
38 °C

Procedure

To methyl 5-(benzoyloxy)-2-{(2S,4R)-1-[(benzyloxy)carbonyl]-4-methoxypyrrolidin-2-yl}-6-hydroxypyrimidine-4-carboxylate, dissolved in dioxane, LiH (1.4 eq.) was added and the reaction mixture stirred at 38° C. for 40 minutes. The temperature was raised to 60° C. and dimethyl sulphate (1.3 eq.) was added dropwise. After two hours the reaction mixture was cooled down to 0° C. and HCl 1 N was added to quench the reaction. The reaction mixture was extracted with ethyl acetate and the organic phase washed with HCl 1N, saturated aqueous NaHCO3 and brine, dried on Na2SO4, filtered and concentrated in vacuo. The desired product was isolated by flash chromatography on silica gel (eluent ethyl acetate: petroleum ether=30:70) as a 1:1 mixture of rotamers by NMR:

Workup

  1. temperatureThe temperature was raised to 60° C.
  2. temperatureAfter two hours the reaction mixture was cooled down to 0° C.
  3. customto quench
  4. customthe reaction
  5. extractionThe reaction mixture was extracted with ethyl acetate
  6. washthe organic phase washed with HCl 1N, saturated aqueous NaHCO3 and brine
  7. customdried on Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-19b24e2ef436496ab7539c2c85f7aee8
Source dataset
uspto-grants-2010_10
Patent number
US07820660B2

Reaction notes

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