Water → HCID 86623503, compound

To a tap-water cooled suspension of 5-benzyloxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one (1.81 g, 5.8 mmol) in dichloromethane (95 mL) was added triethylamine (0.80 mL, 5.8 mmol) dropwise, followed by methanesulfonyl chloride (0.45 mL, 5.8 mmol). The suspension cleared and a slightly cloudy solution was obtained. The progress of the reaction was monitored by HPLC Method 1 (Example 24), which indicated about 75% conversion at this time. Another portion of triethylamine (0.30 mL, 2.1 mmol) and methanesulfonyl chloride (0.160 mL, 2.1 mmol) was added to the reaction mixture, and a bright yellow clear solution resulted. The reaction was completed within 10 min after the addition. The resulting solution was washed with a brine solution (2×50 mL). The organic layer was dried over Na2SO4, and then filtered. To the filtrate was added morpholine polymer-bound beads (1% cross-linked w/DVB, 200-400 mesh, 2.5-4.0 mmol N/g, 4.3 g), and the mixture was vortexed for 1 h. The solid morpholine beads were removed by filtration. The filtrate was evaporated to dryness, and the residual oil was taken up in dichloromethane and ethyl ether, and a solid product was obtained upon stirring. A first crop of the title compound was collected by filtration (1.80 g, 80% yield, HPLC Method 1 (Example 24); RT=15.0 min, HPLC purity (peak percent area): 99.3% at λ=280 nm). 1H NMR (DMSO-d6) δ ppm: 7.77 (s, 1H), 7.40 (m, 5H), 6.61 (q, J=6 Hz, 1H), 6.43 (s, 1H), 5.01 (s, 2H), 3.77 (s, 3H), 3.50 (s, 3H).

1. customa slightly cloudy solution was obtained
2. customa bright yellow clear solution resulted
3. additionafter the addition
4. washThe resulting solution was washed with a brine solution (2×50 mL)
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. additionTo the filtrate was added morpholine polymer-bound beads (1% cross-linked w/DVB, 200-400 mesh, 2.5-4.0 mmol N/g, 4.3 g)
8. waitthe mixture was vortexed for 1 h
9. customThe solid morpholine beads were removed by filtration
10. customThe filtrate was evaporated to dryness
11. customethyl ether, and a solid product was obtained
12. filtrationA first crop of the title compound was collected by filtration (1.80 g, 80% yield, HPLC Method 1 (Example 24); RT=15.0 min, HPLC purity (peak percent area): 99.3% at λ=280 nm)

ORD record

ord-cc026bb2319143b4a3ae4b60611b75f1

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08026261B2