Dimethyl malonate → 2-(2,6-Dimethoxy-5-methylsulfanyl-pyrimidin-4-yl)-malonic acid dimethyl ester

HRID 629023Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-chloro-2,6-dimethoxy-5-methylsulfanyl-pyrimidine (3.30 g, 15.0 mmol.) and dimethyl malonate (11.88 g, 90.0 mmol, 6.0 eq.) was added dropwise to slurry of sodium hydride (60% w/w) (3.67 g, 90.0 mmol, 6.0 eq) in DMF (80 ml) in ice bath at 0° C., then the reaction mixture was stirred at 100° C. for 10 hrs and dried, and the solvent was evaporated. The reaction mixture was partitioned between EA and 0.1 N HCl. The organic layer was washed with brine, dried over MgSO4, filtered and evaporated in vacuo. The resulting residue was purified by flash chromatography on silica gel (Hexane/EtOAc 6:1) to give a pale yellow oil product of 2.85 g (60.2%).

Workup

additionwas added dropwise
customat 0° C.
customdried
customthe solvent was evaporated
customThe reaction mixture was partitioned between EA and 0.1 N HCl
washThe organic layer was washed with brine
dry with materialdried over MgSO4
filtrationfiltered
customevaporated in vacuo
customThe resulting residue was purified by flash chromatography on silica gel (Hexane/EtOAc 6:1)
customto give a pale yellow oil product of 2.85 g (60.2%)

Sources & evidence

ORD record: ord-14cdb2de87db4545a854fed979f52e61
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315491B2

Reaction notes

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