Triethylamine → HCID 11370865, compound

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.

1. customconsumption of the starting material
2. customThe balloon of hydrogen was then removed
3. stirringThe reaction mixture was stirred an additional 9 h
4. filtrationthe resulting black suspension was filtered through Celite
5. customA portion of the solvent was then removed in vacuo
6. additionThe remaining solution (100 mL) was treated with water (150 mL) and EtOAc (100 mL)
7. customThe organic layer was removed
8. additionthe aqueous layer was then carefully acidified by the addition of an aqueous solution of HCl (2M)
9. extractionThe aqueous layer was extracted with EtOAc (5×80 mL)
10. washthe combined organic extracts were then washed with an aqueous solution of HCl (0.1 M, 4×200 mL), brine (200 mL)
11. dry with materialdried over magnesium sulfate
12. customRemoval of the solvent in vacuo

ORD record

ord-0c53429512294f4684a7b21bb258d45b

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067698B2