Dichloromethane → HCID 12112446, Verbindung

To a solution of 1,1,1-trifluoro-2-hydroxy-2-(2-aminophenyl)ethane from Step 2 (600 mg, 3.14 mmol), methylene chloride (10 mL) was added N,N,-diisopropylethylamine (893 mg, 6.91 mmol) followed by 2-furoyl chloride (902 mg, 6.91 mmol) dropwise over 5 min under an argon atmosphere at 23° C. After 18 h, the reaction was diluted with ether (100 mL), washed with KHSO4 (1N, 1×80 mL), sat'd NaHCO3 (1×80 mL), brine (1×80 mL) and dried (MgSO4). After concentration in vacuo, the crude residue was taken on to the next step. The residue was dissolved in ethyl acetate (300 mL), washed with KHSO4 (2×50 mL) and with brine (1×50 mL), dried (Na2SO4), and concentrated in vacuo. To a solution of the residue and methanol (3 mL) was added NaOH (1.5 N, 3 mL) at 23° C. under argon. After 2 h at 23° C., the reaction was concentrated in vacuo, diluted with ether (150 mL), washed with brine (100 mL) and dried (MgSO4). After concentration in vacuo, the residue was purified by flash chromatography (ethyl acetate:hexane 1:3) to afford N-[2-(2,2,2-trifluoro-1-hydroxyethyl)phenyl]furan-2-carboxamide (717 mg, 80%) as an oil: 1H NMR (CDCl3) δ 5.14 (q, J=6 Hz), 6.55 (m), 7.16-7.58 (m), 8.25 (m); 13C NMR (CDCl3) 72.7 (q, J=33 Hz), 112.2, 115.0, 122.7, 123.1, 126.5 (q, J=280 Hz), 129.7, 136.8, 144.7, 149.5, 169.6. MS (EI) 285 (M+), 245, 216. IR (neat) 3500-3000, 1650 cm−1. Anal. Calc'd. for C13H10NO3F3: C, 54.74; H, 3.53; N, 4.91. Found: C, 54.63; H, 3.50; N, 4.90.

1. washwashed with KHSO4 (1N, 1×80 mL), sat'd NaHCO3 (1×80 mL), brine (1×80 mL)
2. dry with materialdried (MgSO4)
3. concentrationAfter concentration in vacuo
4. dissolutionThe residue was dissolved in ethyl acetate (300 mL)
5. washwashed with KHSO4 (2×50 mL) and with brine (1×50 mL)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated in vacuo
8. additionTo a solution of the residue and methanol (3 mL) was added NaOH (1.5 N, 3 mL) at 23° C. under argon
9. waitAfter 2 h at 23° C.
10. concentrationthe reaction was concentrated in vacuo
11. additiondiluted with ether (150 mL)
12. washwashed with brine (100 mL)
13. dry with materialdried (MgSO4)
14. concentrationAfter concentration in vacuo
15. customthe residue was purified by flash chromatography (ethyl acetate:hexane 1:3)

ORD-Eintrag

ord-c27bd927aa544b009185553b6b1a3892

Quelldatensatz

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06673784B1