Potassium Phosphate, Tribasic → Ethyl (3,5-dichloropyridin-2-yl)(difluoro)acetate

HRID 623308Notes

Reaction equation

Br[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1.Br[C:11]([F:18])([F:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.O.[Cu]>[Cl:8][C:7]1[C:2]([C:11]([F:18])([F:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:3][CH:4]=[C:5]([Cl:9])[CH:6]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 56 g (0.246 mol) of 2-bromo-3,5-dichloropyridine in 500 mL of dry dimethylsulfoxide, were added 53 g (0.261 mol) of ethyl bromodifluoroacetate followed by 94 g (0.518 mol) of copper bronze (200 mesh). The beige suspension was heated at 50° C. for 5 hours. After cooling of the reaction mixture, a solution of 44 g (0.328 mol) of potassium monophosphate in 280 mL of water was added and stirred for 1 hour. The black mixture was then filtered over a cake of Supercel™, and the cake was washed three times by 200 mL of ethyl acetate. The organic phases were collected, washed with brine and dried over magnesium sulfate. Evaporation of the solvent under vacuum gave 57.6 g of brown oil. After purification by column chromatography on silica gel (heptane/ethyl acetate 9/1) 40 g (57%) of ethyl (3,5-dichloropyridin-2-yl)(difluoro)acetate (Int-7) were obtained as a yellow oil, (M+1)=270, 19F-NMR (235 MHz, CDCl3) δ (ppm): −104.21 (CF2).

Workup

temperatureAfter cooling of the reaction mixture
filtrationThe black mixture was then filtered over a cake of Supercel™
washthe cake was washed three times by 200 mL of ethyl acetate
customThe organic phases were collected
washwashed with brine
dry with materialdried over magnesium sulfate
customEvaporation of the solvent under vacuum

Sources & evidence

ORD record: ord-6943b37c40454913bd5432140eaf993a
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09301526B2

Reaction notes

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