Chlorotrimethylsilane → HCID 58920497, compound

To an oven-dried round bottomed flask was added 2-methylfuran (0.5 mL, 5.58 mmol) in Et2O (4 mL) at −30° C. nBuLi (2.5 M in hexanes, 0.95 ml, 2.38 mmol, 1.17 eq) was added dropwise at −30° C. under N2. The reaction mixture was slowly warmed up to room temperature and stirred at room temperature overnight. To the resulting light tan solution, cooled at −40° C., was added an Et2O solution (5 mL) of 3-fluoro-5-trifluoromethyl-benzonitrile (1.05 g, 5.58 mmol), added dropwise. The resulting solution was stirred −50 to −10° C. for 3 h. Pretreated TMSCl (0.78 ml, 1.1 eq) was added dropwise at −78° C. The dry ice bath was removed, and the mixture was stirred at r.t. for 1.5 h. It was cooled back to −78° C., and benzylmagnesium chloride (2.7 ml, 5.4 mmol, 0.97 eq) was added dropwise. The resulting mixture was stirred at −78° C. for 30 min, and then at r.t. for 2 h. The reaction mixture was quenched by adding sat'd NH4Cl and 1N HCl, and stirred for 10 min. The resulting solution was extracted with EtOAc, washed with 1N NaOH, sat'd NaHCO3, H2O, brine, dried (MgSO4), filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc, 1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(5-methylfuran-2-yl)-2-phenylethanamine eluted with 15-30% EtOAc in hexanes) to give pure 1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(5-methylfuran-2-yl)-2-phenylethanamine as light brownish gum (1.1 g, yield: 71.4%). LC-MS ESI (10-90% MeOH in H2O with 0.1% TFA in a 4-min run), retention time=3.16 min, 347.13 (M−NH2+H); 1H NMR (400 MHz, CDCl3) δ ppm 7.42 (s, br, 1 H), 7.25 (d, J=10.0 Hz, 1 H), 7.14-7.04 (m, 4 H), 6.77-6.70 (m, 2 H), 5.97 (d, J=3.0 Hz, 1 H), 5.86-5.80 (m, 1 H), 3.41 (d, J=13.2 Hz, 1 H), 3.09 (d, J=13.2 Hz, 1 H), 2.21 (s, 3 H). 1H NMR (xx MHz, CDCl3) δ ppm −63.05 (CF3), −111.53 (F).

1. additionwas added dropwise at −30° C. under N2
2. temperatureTo the resulting light tan solution, cooled at −40° C.
3. additionadded dropwise
4. stirringThe resulting solution was stirred −50 to −10° C. for 3 h
5. customThe dry ice bath was removed
6. stirringthe mixture was stirred at r.t. for 1.5 h
7. temperatureIt was cooled back to −78° C.
8. stirringThe resulting mixture was stirred at −78° C. for 30 min
9. waitat r.t. for 2 h
10. customThe reaction mixture was quenched
11. additionby adding sat'd NH4Cl and 1N HCl
12. stirringstirred for 10 min
13. extractionThe resulting solution was extracted with EtOAc
14. washwashed with 1N NaOH
15. dry with materialdried (MgSO4)
16. filtrationfiltered
17. concentrationconcentrated to dryness
18. customThe residue was purified by flash chromatography (silica gel, hexanes/EtOAc, 1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(5-methylfuran-2-yl)-2-phenylethanamine eluted with 15-30% EtOAc in hexanes)

ORD record

ord-d6b4be25f3404a9788f0e852deadb6d6

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07888376B2