Water → Benzyl 2-(3,5-dichloro-2,6-difluoropyridin-4-yl)acetate

HRID 426295Notes

Reaction equation

HRID 426295 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[N:4][C:5]([F:30])=[C:6]([Cl:29])[C:7]=1[CH:8](C(OCC1C=CC=CC=1)=O)[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].O>CS(C)=O>[Cl:29][C:6]1[C:5]([F:30])=[N:4][C:3]([F:31])=[C:2]([Cl:1])[C:7]=1[CH2:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10]

Participants

4

Reactant 2

HCID 962Water2×HCID 59184667Dibenzyl 2-(3,5-dichloro-2,6-difluoropyridin-4-yl)malonate

Product 1

HCID 59184758Benzyl 2-(3,5-dichloro-2,6-difluoropyridin-4-yl)acetateYield 75%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

3,5-dichloro-2,4,6-trifluoropyridine (25 g, 15.4 mL, 123.7 mmol) and dibenzyl malonate (35.8 g, 31.5 mL, 126 mmol, Aldrich) were dissolved in anhydrous DMF (240 mL) under nitrogen atmosphere. The mixture was then cooled in an ice bath. To a stirred mixture, was added 60% sodium hydride (10 g, 250 mmol) portionwise (2 g) for 2 hr. The mixture was then stirred in a water bath for ca. 17 hr. Glacial acetic acid was added and the mixture was partitioned between ether and water. Ether layer was taken, washed with water twice, dried with anhydrous magnesium sulfate, filtered, and dried in vacuo to give 62 g of dibenzyl 2-(3,5-dichloro-2,6-difluoropyridin-4-yl)malonate as a yellow oil. dibenzyl 2-(3,5-dichloro-2,6-difluoropyridin-4-yl)malonate (62 g) was then dissolved in dimethyl sulfoxide (DMSO) (120 mL) and stirred with water (10 mL) in an oil bath (130-140° C.) for 3 hr. After cooling to room temperature, water was added to the mixture and the product was extracted with ether (Sometimes addition of EA is necessary to dissolve product completely). The ether layer was washed with water twice, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo to give a light yellow solid. The crude product was recrystallized from MC/Hexane three times to afford 30.9 g (75% for two steps) of benzyl 2-(3,5-dichloro-2,6-difluoropyridin-4-yl)acetate as a white solid. m.p. 98-101° C. 1H NMR (200 MHz, CDCl3) δ 4.11 (2H, s), 5.19 (2H, s), 7.30-7.38 (5H, m).

Workup

  1. extractionthe product was extracted with ether (
  2. additionSometimes addition of EA
  3. dissolutionto dissolve product completely)
  4. washThe ether layer was washed with water twice
  5. dry with materialdried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto give a light yellow solid
  9. customThe crude product was recrystallized from MC/Hexane three times

Sources & evidence

ORD record
ord-0a235809d088485c8aaebffcb906c40a
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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