Triethylamine → tert-Butyl 4-(2-(2,4-Difluorophenyl)acetyl)piperazine-1-carboxylate

2-(2,4-Difluorophenyl)acetic acid (5.00 g, 29.1 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (4.46 g, 29.1 mmol), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (5.57 g, 29.1 mmol) and triethylamine (4.05 mL, 29.1 mmol) were stirred in DCM (30 mL) for 15 min. tert-Butyl piperazine-1-carboxylate (2.71 g, 14.5 mmol) was added and the mixture was stirred at room temperature for 8 h. The reaction was diluted with DCM (10 mL) and washed with 1 N NaOH (5 mL), followed by 1 M citric acid (5 mL). The organic extracts were dried over Na2SO4, filtered and concentrated to afford an oil that was purified by RP-HPLC. The best fractions were lyophilized to afford material that was neutralized with NaHCO3 (75 mL), and extracted with EtOAc (2×200 mL). The organic extracts were dried over Na2SO4, filtered, and concentrated to afford the title compound (1.68 g) as a yellow solid. 1H NMR (DMSO-d6, 400 MHz) δ 1.42 (s, 9H), 3.25-3.39 (m, 4H), 3.42-3.48 (m, 2H), 3.49-3.56 (m, 2H), 3.74 (s, 2H), 7.02 (dt, J=2.7, 8.5 Hz, 1H), 7.18 (dt, J=2.6, 9.7 Hz, 1H), 7.25-7.33 (m, 1H). Exact mass calculated for C17H22F2N2O3: 340.2. Found: LCMS m/z=341.3 (M+H+).

1. additionwas added
2. washwashed with 1 N NaOH (5 mL)
3. dry with materialThe organic extracts were dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customto afford an oil that
7. customwas purified by RP-HPLC
8. customto afford material that
9. extractionextracted with EtOAc (2×200 mL)
10. dry with materialThe organic extracts were dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated

ORD-Eintrag

ord-65f7a883964549cab03146e04ef7bb35

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09434692B2