Hydrochloric Acid → 2-(4,6-Dimethoxypyrimidine-2-yl)-2-(3-methoxymethyl-2-nitrophenyl)acetonitrile

HRID 989601

Reaction equation

[H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[N:8]=[C:7]([CH2:13][C:14]#[N:15])[N:6]=1.[H][H].Cl[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][O:26][CH3:27])[C:20]=1[N+:28]([O-:30])=[O:29].Cl>CN(C)C=O>[CH3:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[N:8]=[C:7]([CH:13]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][O:26][CH3:27])[C:20]=2[N+:28]([O-:30])=[O:29])[C:14]#[N:15])[N:6]=1

Participants

Conditions

Temperature: 10 °C

Procedure

11.2 g (0.28 M) of 60% sodium hydride was suspended in 100 ml of N,N-dimethylformamide. While the suspension was cooled to 10° C. or lower in an ice water bath and stirred, thereto was dropwise added a solution of 25 g (0.14 M) of 2-(4,6-dimethoxypyrimidine-2-yl)acetonitrile dissolved in 100 ml of N,N-dimethylformamide. After the completion of the dropwise addition, the mixture was stirred at room temperature until there was no evolution of hydrogen. While the mixture was cooled to 10° C. or lower in an ice water bath and stirred, thereto was dropwise added a solution of 28 g (0.14 M) of 2-chloro-6-methoxymethylnitrobenzene dissolved in 100 ml of dimethylformamide. Then, the mixture was stirred at room temperature for 12 hours. The reaction mixture was poured into ice water. The mixture was acidified with 10% hydrochloric acid, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and water, dried and concentrated under reduced pressure. The resulting crystals were washed with a mixed solvent of ethanol and isopropyl ether to obtain 31 g (yield: 64%) of 2-(4,6-dimethoxypyrimidine-2-yl)-2-(3-methoxymethyl-2-nitrophenyl)acetonitrile as a reddish brown powder (melting point: 112 to 113° C).

Workup

additionAfter the completion of the dropwise addition
stirringthe mixture was stirred at room temperature until there
temperatureWhile the mixture was cooled to 10° C. or lower in an ice water bath
stirringstirred
stirringThen, the mixture was stirred at room temperature for 12 hours
extractionfollowed by extraction with ethyl acetate
washThe organic layer was washed with a saturated aqueous sodium chloride solution and water
customdried
concentrationconcentrated under reduced pressure
washThe resulting crystals were washed with a mixed solvent of ethanol and isopropyl ether

Sources & evidence

ORD record: ord-150bb4e92c8b41b2800be221570dafcc
Source dataset: uspto-grants-2002_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06458748B1

Linked notes

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