Triethylamine → HCID 11370865, compound

Participants

Reaction Steps

To a degassed solution of acid 4 (25 g, 68 mmol) in MeOH (250 mL) was added Pd/C (10% Pd, 350 mg, 0.33 mmol) followed by hydrogen gas (1 atm, balloon). The reaction mixture was stirred at RT for 12 h by which time TLC showed complete consumption of the starting material. The balloon of hydrogen was then removed and MeOH (100 mL), ethyl trifluoroacetate (14.6 g, 103 mmol), and Et3N (13.8 g, 136 mmol) were added. The reaction mixture was stirred an additional 9 h and the resulting black suspension was filtered through Celite. A portion of the solvent was then removed in vacuo. The remaining solution (100 mL) was treated with water (150 mL) and EtOAc (100 mL). The organic layer was removed and the aqueous layer was then carefully acidified by the addition of an aqueous solution of HCl (2M). The aqueous layer was extracted with EtOAc (5×80 mL), and the combined organic extracts were then washed with an aqueous solution of HCl (0.1 M, 4×200 mL), brine (200 mL), and dried over magnesium sulfate. Removal of the solvent in vacuo gave the desired product 6 as a viscous oil (22.4 g, 68 mmol, quantitative yield): (Sakarellos et al., J. Org. Chem. 43: 293–296 (1978), viscous oil); Rf=0.65 (65:31:4 EtOAc/hexane/AcOH); 1H NMR (300 MHz, D6-DMSO) δ 12.50 (br s, 1 H), 9.41 (t, 1 H, J=3.2 Hz), 7.11 (d, 1 H, J=4.8 Hz), 3.84–3.87 (m, 1 H), 3.15–3.19 (m, 2 H), 1.51–1.69 (m, 4 H), 1.38 (s, 9 H) ppm; 13C NMR (75 MHz, D6-DMSO) δ 174.1, 156.2 (q, J=35 Hz), 155.7, 116.0 (q, J=286 Hz), 78.1, 53.2, 38.9, 28.2, 25.2 ppm; IR (thin film) 3316, 1709 cm−1; HRMS calculated (M-Boc, C7H10F3N2O3) 227.0644. found 227.0658.

Provenance & Evidence