Ethyl Acrylate → Ethyl (E)-3-(2-chloropyrimidin-5-yl)acrylate

HRID 508651Notes

Reaction equation

HRID 508651 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[C:9]([O:13][CH2:14][CH3:15])(=[O:12])[CH:10]=[CH2:11].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C)C=O.C(N(C(C)C)CC)(C)C.[Cl-].[Na+].O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[Cl:8][C:5]1[N:4]=[CH:3][C:2](/[CH:11]=[CH:10]/[C:9]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7][N:6]=1

Participants

8

Reactant 3

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 6066655-Bromo-2-chloropyrimidine

Product 1

HCID 53259409Ethyl (E)-3-(2-chloropyrimidin-5-yl)acrylateYield 73.7%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 5-bromo-2-chloropyrimidine (4.03 g, 20.8 mmol), ethyl acrylate (9.06 mL, 83.3 mmol), palladium diacetate (187 mg, 0.830 mmol) and tri(o-tolyl)phosphine (762 mg, 2.50 mmol) in dimethylformamide (22 mL) and diisopropylethylamine (11 mL) was heated at reflux for 3.5 h, then cooled to room temperature and diluted with brine. The suspension was extracted with ethyl acetate. The extract was washed (brine) and dried. After solvent removal at reduced pressure, the residue was chromatographed (silica gel, 11% ethyl acetate/hexane) to give 3.26 g (73%) of ethyl(E)-3-(2-chloro-5-pyrimidinyl)-2-propenoate as a yellow solid, mp 125-127° C. IR 2905, 1698, 1542, 1405, 1160 cm−1; 1H NMR (CDCl3) δ 1.38 (t, J=7.2 Hz, 3H, OCH2CH3), 4.32 (q, J=7.2 Hz, 2H, OCH2CH3), 6.60 (d, J=16.2 Hz, 1H, CH═CHCO), 7.61 (d, J=16.2 Hz, 1H, CH═CHCO), 8.79 (s, 2H, 4-PyrH, 6-PyrH). HRMS calcd C9H9ClN2O2 [M+H]+ 213.0425. found 213.0428.

Workup

  1. temperatureat reflux for 3.5 h
  2. extractionThe suspension was extracted with ethyl acetate
  3. washThe extract was washed (brine)
  4. customdried
  5. customAfter solvent removal at reduced pressure
  6. customthe residue was chromatographed (silica gel, 11% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-ba05ffaf851f41caaebf469d2e926217
Source dataset
uspto-grants-2015_08
Patent number
US09096544B2

Reaction notes

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