Sulfuric Acid → HCID 21930302, compound

3-(Trifluoromethoxy)phenol (4.827 g, 27 mmol) was dissolved in glacial acetic acid (20 mL). The mixture was cooled in an ice bath between 14–17° C. and concentrated sulfuric acid (2 mL) was slowly added keeping the temperature below 20° C. The mixture was cooled below 10° C. and N-hydroxymethyl-2-chloroacetamide (3.52 g, 28.5 mmol) was added. The mixture was warmed slowly to room temperature and stirred overnight. The mixture was then poured slowly into ice (200 mL) and the pH was adjusted to ˜4–5 with KOH pellets, keeping the temperature below 5° C. The reaction mixture was warmed to room temperature and extracted twice with ethyl acetate (150 mL). The organic layer was collected and washed with NaHCO3 (sat., 30 mL). The organic layer was dried over MgSO4, filtered and the solvent removed to dryness. The mixture was purified by column chromatography (SiO2, 700 mL) using an eluent of hexane/ethyl acetate (10/2). Recovery: 2.42 g (33.8% yield). 1H NMR (DMSO) δ=10.23 (1H, s), 8.56 (1H, st), 7.16–7.14 (1H, sd), 6.71–6.70 (2H, br), 4.18–4.17 (2H, d), 4.08 (2H, s).

1. temperatureThe mixture was cooled in an ice bath between 14–17° C.
2. customthe temperature below 20° C
3. temperatureThe mixture was cooled below 10° C.
4. customthe temperature below 5° C
5. temperatureThe reaction mixture was warmed to room temperature
6. extractionextracted twice with ethyl acetate (150 mL)
7. customThe organic layer was collected
8. washwashed with NaHCO3 (sat., 30 mL)
9. dry with materialThe organic layer was dried over MgSO4
10. filtrationfiltered
11. customthe solvent removed to dryness
12. customThe mixture was purified by column chromatography (SiO2, 700 mL)

ORD record

ord-f45f715471be42358b00ac93c06a0cfc

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07119120B2