Diisopropylethylamine → HCID 58374159, compound

Participants

Reaction Conditions

Reaction Steps

(S)-Ethyl-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-((Z)-N′-hydroxycarbamimidoyl)phenyl)ethyl)piperidine-3-carboxylate (32.6 g, 72 5 mmol) was dissolved in acetonitrile (145 ml) (anhydrous) and cooled to ˜3° C. with ice-bath. 3-phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl chloride (19.98 g, 72.5 mmol) was dissolved in 50 mL anhydrous acetonitrile and added dropwise. The internal temperature was kept below 10° C. during addition. After addition, the reaction mixture was allowed to warm to room temperature. At 30 minutes, HPLC showed completion of the first reaction step. The reaction mixture was re-cooled to below 10° C. DIEA (18.99 ml, 109 mmol) was added slowly. After the addition, the reaction mixture was heated up to 55° C. for 17 hrs. HPLC/LCMS showed completion of the reaction. The solvents were removed by ROTAVAPOR®. The residue was stirred in 250 mL 20% EtOAc/hexanes and the DIPEA HCl salt precipitated from solution and was removed via filtration. The filtrate was concentrated and purified using a silica gel cartridge (3×330 g silica, 0-50% EtOAc/hexanes gradient). (S)-ethyl 1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate (43g, 64.1 mmol, 88% yield) was obtained a light yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.16 (2H, d), 7.68 (2H, d), 7.57 (5H, m), 4.85 (1H, m), 4.14 (2H, m), 2.95 (1H, m), 2.82 (1H, m), 2.64 (1H, dd), 2.51 (1H, m), 2.49 (1H, dd), 2.35 (1H, tt), 2.14 (1H, dt), 1.91 (1H, m), 1.66 (1H, dt), 1.57 (1H, m), 1.48 (1H, m), 1.27 (3H, t), 0.92 (9H, s), 0.11 (3H, s), −0.05 (3H, s).

Provenance & Evidence