4-Bromo-3-fluorobenzaldehyde → (E)-5-(4-bromo-3-fluorophenyl)pent-4-enoic acid

To a solution of 3-carboxypropyltriphenylphosphonium bromide (8.6 g, 20 mmol) in DMSO (20 mL) was added solid KOt-Bu (4.49 g, 40.0 mmol) at rt. After stirring for 40 min, a solution of 4-bromo-3-fluorobenzaldehyde (3.45 g, 17.00 mmol) in DMSO was added slowly. The mixture was stirred at rt for 16 h. The reaction was quenched with water (200 mL), washed with EtOAc/hexanes (1/1). The aqueous layer was neutralized with concentrated hydrochloric acid to pH=2, extracted with EtOAc. The organic layer was concentrated. The residue was purified by silica gel column chromatography (hexanes-100% EtOAc) to give (E)-5-(4-bromo-3-fluorophenyl)pent-4-enoic acid (2.2 g, 8.06 mmol, 40% yield). LCMS (M−H)−=273.1. 1H NMR (500 HMz, chloroform-d) δ 7.47 (dd, J=8.2, 7.2 Hz, 1H), 7.12 (dd, J=9.9, 2.0 Hz, 1H), 7.00 (dd, J=8.2, 2.0 Hz, 1H), 6.41-6.36 (m, 1H), 6.29-6.22 (m, 1H), 2.58-2.56 (m, 4H).

1. stirringThe mixture was stirred at rt for 16 h
2. customThe reaction was quenched with water (200 mL)
3. washwashed with EtOAc/hexanes (1/1)
4. extractionextracted with EtOAc
5. concentrationThe organic layer was concentrated
6. customThe residue was purified by silica gel column chromatography (hexanes-100% EtOAc)

ORD record

ord-07da6d07d6b0461286493dd7151fd613

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604024B2