Chlorotrimethylsilane → HCID 58921424, compound

Participants

Reaction Conditions

Reaction Steps

To an oven-dried round bottomed flask cooled at −78° C. under N2, was added anhydrous Et2O (15 mL) and nBuLi (1.6 M in hexanes, 2.5 mL, 4.0 mmol, 1 eq.) sequentially. An Et2O solution (3 mL) of 2-bromothiazole (0.66 g, 4.0 mmol) was added to the above solution at −78° C. dropwise. The resulting solution was stirred at −78° C. to −70° C. for 20 min. To the lightly pale yellow solution, was added 3-fluoro-5-trifluoromethyl-benzonitrile in THF (2 mL) dropwise at −78° C. The resulting mixture was stirred at −78 to −70° C. for 2.5 h. Pretreated TMSCl (10:1 v/v TMSCl:Et3N, then centrifuge at r.t. for 15 min, 0.51 mL of the clear solution, 1.01 eq) was added to the stirred mixture dropwise at −78° C. The resulting mixture was stirred at −78 to −60° C. for 15 min, then room temperature for 30 min, during which period the solution changed from dark brown to light tan. The reaction mixture was cooled back to −78° C., benzyl magnesium chloride (2.0 M in THF, 2.0 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 15 min, then gradually warmed up to room temperature for 1.5 h. The reaction mixture was quenched by adding sat'd NH4Cl and 1 N HCl, and stirred for 20 min. The resulting crude reaction mixture was extracted with EtOAc, washed with 1N NaOH, sat'd NaHCO3, H2O, brine, dried over MgSO4, filtered, and concentrated to dryness in vacuo. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc, came out 20% EtOAc) to give racemic 1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenyl-1-(thiazol-2-yl)ethanamine as light brownish viscous oil (0.35 g, yield: 24%). LC-MS ESI (10-90% MeOH in H2O with 0.1% TFA in a 4-min run), retention time=2.97 min 367.04 (M+H), 350.02 (M−NH3). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 7.78 (d, J=3.18 Hz, 1 H), 7.66 (s, 1 H), 7.52-7.61 (m, 1 H), 7.08-7.19 (m, 5 H), 6.82 (dd, J=7.6, 2.0 Hz, 2 H), 3.86 (d, J=13.2 Hz, 1 H), 3.35 (d, J=13.2 Hz, 1 H).

Provenance & Evidence