Sodium hydride → (5-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate

HRID 1162205Notes

Reaction equation

[H-].[Na+].[CH3:3][O:4][C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[C:7](=[O:15])[NH:8][CH:9]=[N:10]2.[C:16]([O:22][CH2:23]Cl)(=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18]>CN(C=O)C>[C:16]([O:22][CH2:23][N:8]1[C:7](=[O:15])[C:6]2[C:11](=[CH:12][CH:13]=[CH:14][C:5]=2[O:4][CH3:3])[N:10]=[CH:9]1)(=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: 25 °C

Procedure

Sodium hydride (1.24 g, 60% in oil, 31 mmol) was added portion-wise to a solution of 5-methoxyquinazolin-4(3H)-one (5 g, 28.4 mmol; obtained as described in WO-96/09294) in anhydrous DMF (50 ml) while maintaining the temperature at 25° C. The mixture was stirred at room temperature for 30 minutes. Chloromethyl pivalate (4.45 ml, 31 mmol) was added at room temperature for 3 hours. Additional sodium hydride (0.12 g, 3 mmol) and chloromethyl pivalate (0.67 ml, 4.5 mmol) were added and the mixture was stirred another hour. After evaporation of the solvents under high vacuum, the mixture was diluted with water and extracted with DCM. After drying with magnesium sulfate and evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: ethyl acetate-petroleum ether, 6:4 to 8:2) to give (5-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate as a white solid (7.4 g, 90%); HPLC tR: 2.69 min; Mass spectrum MH+ 291.

Workup

customobtained
stirringthe mixture was stirred another hour
customAfter evaporation of the solvents under high vacuum
additionthe mixture was diluted with water
extractionextracted with DCM
dry with materialAfter drying with magnesium sulfate and evaporation of the solvents
customthe residue was purified by chromatography on silica gel (eluant: ethyl acetate-petroleum ether, 6:4 to 8:2)

Sources & evidence

ORD record: ord-cf3484ae2a9d4238951886dda1a91d04
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820683B2

Reaction notes

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