Acetic Acid → HCID 118342833, compound

To a solution of crude 2-(2,6-dichloro-3-fluorophenyl)-2-((trimethylsilyl)oxy)acetaldehyde (0.258 g, 0.874 mmol) in MeCN (9 ml) was added (1-(trifluoromethyl)cyclopropyl)methanamine (0.122 g, 0.874 mmol) followed by AcOH (0.050 ml, 0.874 mmol). The reaction mixture was stirred at room temperature for 1 h. Then NaBH(OAc)3 (0.370 g, 1.748 mmol) was added. The reaction mixture was stirred at room temperature for 23 h. Then it was quenched by adding saturated aqueous NaHCO3 solution and stirred for 30 min. It was extracted with DCM (2×5 mL). The combined organic layer washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure to provide a yellow oil. The yellow oil was dissolved in 2 mL of THF. Then TBAF, 1.0 M solution in THF (0.874 ml, 0.874 mmol) was added. The reaction mixture was stirred at room temperature for 15 min. It was quenched with saturated aqueous NaHCO3 and extracted with DCM. The combined organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, eluent: 0% to 50% EtOAc/heptane) to provide 1-(2,6-dichloro-3-fluorophenyl)-2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)ethanol (116 mg, 0.335 mmol, 38.3% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.25-7.31 (m, 1H), 7.06 (dd, J=8.9, 8.0 Hz, 1H), 5.45 (dd, J=9.7, 4.5 Hz, 1H), 3.45 (br. s., 1H), 3.28 (dd, J=12.6, 9.8 Hz, 1H), 2.89-2.92 (m, 3H), 0.99-1.04 (m, 2H), 0.69-0.76 (m, 2H); LCMS: 346.0 [M+H]+.

1. stirringThe reaction mixture was stirred at room temperature for 23 h
2. customThen it was quenched
3. additionby adding saturated aqueous NaHCO3 solution
4. stirringstirred for 30 min
5. extractionIt was extracted with DCM (2×5 mL)
6. washThe combined organic layer washed with brine
7. dry with materialdried over anhydrous MgSO4
8. concentrationconcentrated under reduced pressure
9. customto provide a yellow oil
10. stirringThe reaction mixture was stirred at room temperature for 15 min
11. customIt was quenched with saturated aqueous NaHCO3
12. extractionextracted with DCM
13. dry with materialThe combined organic layer was dried over anhydrous MgSO4
14. concentrationconcentrated under reduced pressure
15. customThe crude material was purified by column chromatography (silica gel, eluent: 0% to 50% EtOAc/heptane)

ORD record

ord-1984c24866b9495ca70060f7e1710b13

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365522B2