Chlorotrimethylsilane → HCID 58919981, compound

Temperature

-78 °C

To an oven-dried round bottomed flask was added nBuLi (2.5 M in hexanes, 0.95 ml, 2.38 mmol, 1.17 eq) at −60° C. under N2. An Et2O solution (5 mL) of 2-bromo-4-trifluoromethylpyridine (448 mg, 2.0 mmol) was added dropwise at −60 to −55° C. The resulting solution was stirred at the above temperate for 30 min. The mixture was cooled to −78° C., an Et2O solution (2 mL) of 3-fluoro-5-trifluoromethyl-benzonitrile (390 g, 2.06 mmol) was added dropwise. The resulting solution was stirred −78 to −70° C. for 1.5 h. Pretreated TMSCl (0.26 ml) was added dropwise at −78° C. The mixture was stirred at −78° C. for 15 min, and then warmed up to r.t. for 45 min. It was cooled back to −78° C., and benzyl magnesium chloride (1.0 ml, 2.0 mmol) was added dropwise. The resulting mixture was stirred at −78° C. for 1 h, and then at r.t. for 0.5 h. It was quenched by adding sat'd NH4Cl and 1N HCl, and stirred for 10 min. It 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) to give 1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenyl-1-(4-(trifluoromethyl)pyridin-2-yl)ethanamine as light brownish gum (0.57 g, yield: 66.6%). LC-MS ESI (10-90% MeOH in H2O with 0.1% TFA in a 4-min run), retention time=3.32 min, 429.13 (M+H).

1. stirringThe resulting solution was stirred −78 to −70° C. for 1.5 h
2. stirringThe mixture was stirred at −78° C. for 15 min
3. temperaturewarmed up to r.t. for 45 min
4. temperatureIt was cooled back to −78° C.
5. stirringThe resulting mixture was stirred at −78° C. for 1 h
6. waitat r.t. for 0.5 h
7. customIt was quenched
8. additionby adding sat'd NH4Cl and 1N HCl
9. stirringstirred for 10 min
10. extractionIt was extracted with EtOAc
11. washwashed with 1N NaOH
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated to dryness
15. customThe residue was purified by flash chromatography (silica gel, hexanes/EtOAc)

ORD record

ord-fd17d3c4882a4c18925912fbcb99db10

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07888376B2