Methyl Acrylate → (E)-methyl 3-(3,5-difluoro-4-formylphenyl)acrylate

Temperature

80 °C

4-Bromo-2,6-difluorobenzaldehyde (9.99 g, 45.20 mmol) and methyl acrylate (6.14 ml, 67.81 mmol) were taken up in thoroughly degassed DMA (100 ml) and tri-o-tolylphosphine (1.376 g, 4.52 mmol), palladium(II) acetate (0.507 g. 2.26 mmol) and triethylamine (12.60 ml, 90.41 mmol) added. The reaction was stirred and heated to 80° C. for 6 hours. The reaction mixture was cooled and filtered through a layer of celite, and washed with methanol (50 ml). The crude product was pre-absorbed onto silica and purified by suction chromatography eluting with 0-10% diethyl ether/dichloromethane. Fractions containing the desired product were evaporated and triturated with diethyl ether (50 ml) to afford a yellow solid which was triturated with water (50 ml) and dried under high vacuum at 50° C. to afford (E)-methyl 3-(3,5-difluoro-4-formylphenyl)acrylate (8.85 g, 87%) as a yellow solid. 1H NMR (400 MHz, DMSO, 27° C.) δ 3.75 (3H, s), 6.93 (1H, d), 7.52-7.81 (3H, m), 10.18 (1H, s). No mass ion observed in LCMS.

1. additionadded
2. temperatureThe reaction mixture was cooled
3. filtrationfiltered through a layer of celite, and
4. washwashed with methanol (50 ml)
5. customThe crude product was pre-absorbed onto silica
6. custompurified by suction chromatography
7. washeluting with 0-10% diethyl ether/dichloromethane
8. additionFractions containing the desired product
9. customwere evaporated
10. customtriturated with diethyl ether (50 ml)
11. customto afford a yellow solid which
12. customwas triturated with water (50 ml)
13. customdried under high vacuum at 50° C.

ORD record

ord-8e5b1fa48f5845e68175cef291d000c2

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09155727B2