Dimethyl Sulfate → tert-butyl (2R)-2-{[(3-{[(2,2-dimethylpropanoyl)oxy]methyl}-7-methoxy-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate

HRID 640014Notes

Reaction equation

HRID 640014 reaction equation
[C:1](=O)([O-])[O-].[K+].[K+].[CH3:7][C:8]([CH3:40])([CH3:39])[C:9]([O:11][CH2:12][N:13]1[C:22](=[O:23])[C:21]2[C:16](=[CH:17][C:18]([OH:38])=[CH:19][C:20]=2[O:24][CH2:25][C@H:26]2[CH2:30][CH2:29][CH2:28][N:27]2[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:15]=[CH:14]1)=[O:10].S(OC)(OC)(=O)=O>CN(C)C=O>[CH3:7][C:8]([CH3:40])([CH3:39])[C:9]([O:11][CH2:12][N:13]1[C:22](=[O:23])[C:21]2[C:16](=[CH:17][C:18]([O:38][CH3:1])=[CH:19][C:20]=2[O:24][CH2:25][C@H:26]2[CH2:30][CH2:29][CH2:28][N:27]2[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:15]=[CH:14]1)=[O:10]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 86609387tert-butyl (2R)-2-{[(3-{[(2,2-dimethylpropanoyl)oxy]methyl}-7-hydroxy-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate

Product 1

HCID 86609388tert-butyl (2R)-2-{[(3-{[(2,2-dimethylpropanoyl)oxy]methyl}-7-methoxy-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylateYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Potassium carbonate (1.60 g, 12.6 mmol) was added to a solution of tert-butyl (2R)-2-{[(3-{[(2,2-dimethylpropanoyl)oxy]methyl}-7-hydroxy-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate (1.50 g, 3.2 mmol) in dimethylformamide (10 ml) and the mixture stirred at 0° C. for 5 minutes. Dimethyl sulphate (0.6 ml, 6.3 mmol) was added and the reaction stirred at 0° C. for a further 5 minutes and then warmed to room temperature and stirred for 1 hour. The reaction mixture was evaporated under reduced pressure and the residue dissolved in dichloromethane (20 ml) and washed with water (2×20 ml). The organics were dried over magnesium sulphate, filtered and evaporated under reduced pressure to give tert-butyl (2R)-2-{[(3-{[(2,2-dimethylpropanoyl)oxy]methyl}-7-methoxy-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate (0.750 g, 48% yield) which was used in the next stage without further purification.

Workup

  1. stirringthe reaction stirred at 0° C. for a further 5 minutes
  2. temperaturewarmed to room temperature
  3. stirringstirred for 1 hour
  4. customThe reaction mixture was evaporated under reduced pressure
  5. dissolutionthe residue dissolved in dichloromethane (20 ml)
  6. washwashed with water (2×20 ml)
  7. dry with materialThe organics were dried over magnesium sulphate
  8. filtrationfiltered
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-638bb6809d1f44fdb5272da7c18f70e2
Source dataset
uspto-grants-2010_04
Patent number
US07691867B2

Reaction notes

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