Dimethylformamide → (E)-(2-((6-Chloro-5-fluoropyrimidin-4-yl)oxy)phenyl)(5,6-dihydro-1,4,2-dioxazin-3-yl)methanone O-methyl oxime

HRID 716730Notes

Reaction equation

Cl[C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=1.[CH3:10][O:11]/[N:12]=[C:13](/[C:21]1[O:26][CH2:25][CH2:24][O:23][N:22]=1)\[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[OH:20].C([O-])([O-])=O.[K+].[K+].CN(C=O)C>C1(C)C=CC=CC=1>[CH3:10][O:11]/[N:12]=[C:13](/[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=1)\[C:21]1[O:26][CH2:25][CH2:24][O:23][N:22]=1

Participants

Conditions

Temperature: 82.5 °C

Procedure

To a solution of 4,6-dichloro-5-fluoropyrimidine (DCFP) (100 g, 0.564 mol) in toluene (500 mL) was added (E)-(5,6-dihydro-1,4,2-dioxazin-3-yl)(2-hydroxyphenyl)methanone O-methyl oxime (13) (77.8 g, 0.466 mol), K2CO3 (76 g, 0.55 mol), followed by the addition of DMF (50 mL) at ambient temperature. The reaction mixture was stirred at 80-85° C. for 1-2 h. The progress of the reaction was monitored by the HPLC analysis. Upon completion of the reaction, the reaction mixture was washed with water (500 mL) and 10% brine solution (250 mL) to obtain the product in toluene layer meeting the desired specifications. Yield—88-98%.

Workup

customUpon completion of the reaction
washthe reaction mixture was washed with water (500 mL) and 10% brine solution (250 mL)
customto obtain the product in toluene layer

Sources & evidence

ORD record: ord-7e30b064b8684d2087ea3db4fa5fef3f
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193698B2

Reaction notes

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