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

HRID 508664Notes

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=O)C.C(N(C(C)C)CC)(C)C.[Cl-].[Na+].O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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

Conditions

Temperature: 115 °C

Procedure

A solution of 5-bromo-2-chloropyrimidine (4.03 g, 20.8 mmol), ethyl acrylate (9.06 mL, 83.3 mmol), palladium(II) acetate (187 mg, 0.830 mmol), and tri(o-tolyl)phosphine (762 mg, 2.50 mmol) in DMF (22 mL) and diisopropylethylamine (11 mL) was heated at reflux (115° C. oil bath) for 3.5 h, cooled to room temperature, and diluted with brine. The suspension was extracted with EtOAc (300 mL). The extract was washed (brine) and dried. After solvent removal at reduced pressure, the residue was purified on silica gel (11% EtOAc/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-ArH, 6-ArH). HRMS calcd C9H9ClN2O2 [M+H]+ 213.0425. found 213.0428.

Workup

temperaturecooled to room temperature
extractionThe suspension was extracted with EtOAc (300 mL)
washThe extract was washed (brine)
customdried
customAfter solvent removal at reduced pressure
customthe residue was purified on silica gel (11% EtOAc/hexane)

Sources & evidence

ORD record: ord-079d840e49f040d5b88c23dd005da2d1
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096544B2

Reaction notes

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