Boron tribromide → 1-Allyl-2-difluoromethyl-5-hydroxy-1-H-pyridin-4-one

An alternative debenzylation procedure was used for the allyl derivative in order to avoid reduction of the allyl double bond. Thus, a clear yellow/brown solution of 1-allyl-5-benzyloxy-2-difluoromethyl-1H-pyridin-4-one (2.91 g, 10 mmol) in dichloromethane (30 mL) was cooled in an ice-salt bath under a positive nitrogen atmosphere. Then, a pre-mixed 1.0 M boron tribromide solution (10 mL) and dichloromethane (10 mL) was added dropwise. After 20 min, the reaction mixture was quenched with 25 mL of methanol. The solution was concentrated to dryness. The obtained solid was suspended in ether. The solid was collected by filtration to afford the title product (2.65 g, 94% yield) as the hydrobromide salt. HPLC purity (peak area percent) is 99.4% at λ=267 nm using HPLC Method 1 as described above. 1H NMR (400 MHz, DMSO-D6+D2O) δ (ppm): 8.10 (s, 1H), 7.29 (t, J=53.0 Hz, 1H, CF2H), 6.26 (s, 1H), 5.07-6.00 (m, 1H), 5.36 (d, J=10.3 Hz, 1H), 5.20 (d, J=17.1 Hz, 1H), 4.95 (d, J=5.1 Hz, 2H).

1. customthe reaction mixture was quenched with 25 mL of methanol
2. concentrationThe solution was concentrated to dryness
3. filtrationThe solid was collected by filtration

ORD record

ord-2481fb47e7bc4b61be892fe10b700400

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08673943B2