1-(2-aminophenyl)-2,2,2-trifluoroethanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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) δ5.14 (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. washed with KHSO4 (1N, 1×80 mL), sat'd NaHCO3 (1×80 mL), brine (1×80 mL) dried (MgSO4) After concentration in vacuo The residue was dissolved in ethyl acetate (300 mL) washed with KHSO4 (2×50 mL) and with brine (1×50 mL) dried (Na2SO4) 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) dried (MgSO4) After concentration in vacuo the residue was purified by flash chromatography (ethyl acetate:hexane 1:3)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,1,1-trifluoro-2-hydroxy-2-(2-nitrophenyl)ethane from Step 1 (5.45 g, 24.64 mmol) in 90 mL of ethanol was hydrogenated over 200 mg of Raney Nickel at 5 psi hydrogen over a 8 h period at 23° C. After removing the catalyst by filtration, concentration in vacuo afforded a quantitative yield of 1,1,1-trifluoro-2-hydroxy-2-(2-aminophenyl)ethane as a orange-yellow solid: 1H NMR (CDCl3) δ4.32 (br s), 5.03 (q, J=6 Hz), 6.28 (br s), 6.67-6.78 (m), 7.08-7.23 (m); 13C NMR (CDCl3) 66.6 (q, J=33 Hz), 121.9, 124.9, 127.2 (q, J=280 Hz,), 129.3, 130.1, 133.6; MS (EI) 191 (M+), 173, 122. IR (neat) 3395, 3325, 3400-3100. Anal. Calc'd. for C8H8NOF3: C, 50.26; H, 4.22; N, 7.33. Found: C, 50.47; H, 4.57; N, 7.05. After removing the catalyst by filtration, concentration in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. washed with KHSO4 (1N, 1×80 mL), sat'd NaHCO3 (1×80 mL), brine (1×80 mL) dried (MgSO4) After concentration in vacuo The residue was dissolved in ethyl acetate (300 mL) washed with KHSO4 (2×50 mL) and with brine (1×50 mL) dried (Na2SO4) 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) dried (MgSO4) After concentration in vacuo the residue was purified by flash chromatography (ethyl acetate:hexane 1:3)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,1,1-trifluoro-2-hydroxy-2-(2-nitrophenyl)ethane from Step 1 (5.45 g, 24.64 mmol) in 90 mL of ethanol was hydrogenated over 200 mg of Raney Nickel at 5 psi hydrogen over a 8 h period at 23° C. After removing the catalyst by filtration, concentration in vacuo afforded a quantitative yield of 1,1,1-trifluoro-2-hydroxy-2-(2-aminophenyl)ethane as a orange-yellow solid: 1H NMR (CDCl3) δ 4.32 (br s), 5.03 (q, J=6 Hz), 6.28 (br s), 6.67-6.78 (m), 7.08-7.23 (m); 13C NMR (CDCl3) 66.6 (q, J=33 Hz), 121.9, 124.9, 127.2 (q, J=280 Hz), 129.3, 130.1, 133.6; MS (EI) 191 (M+), 173, 122. IR (neat) 3395, 3325, 3400-3100. Anal. Calc'd. for C8H8NOF3: C, 50.26; H, 4.22; N, 7.33. Found: C, 50.47; H, 4.57; N, 7.05. After removing the catalyst by filtration, concentration in vacuo