N,N-diethyl-2,2,2-trifluoroacetamide

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: tert-Butyl 1-(4-bromophenyl)ethylcarbamate (6.35 g, 21.2 mmol) was dissolved in dry THF (100 ml) and cooled to −78° C. under an atmosphere of nitrogen. n-Butyllithium (21 ml, 52.9 mmol, 2.5M in hexanes) was added dropwise under 10 minutes and the reaction was stirred at −78° C. for 3 hours. A solution of diethyl trifluoroacetamide (5.0 g, 29.6 mmol) in 10 ml dry THF was added dropwise and the reaction was stirred 1.5 hours at −78° C. Reaction was quenched with NH4Cl (sat) (50 ml) and H2O (50 ml) and allowed to reach room temperature. The aqueous phase was separated and extracted with EtOAc (100 ml). The combined organics were washed with NH4Cl (sat) (2*100 ml), H2O (100 ml), dried over MgSO4, filtered and evaporated. Unreacted starting material was removed by precipitation from MeOH/H2O (9/1). The mother liquor was evaporated and the residue purified by flash chromatography using Pet. Ether/EtOAc (7:1→5:1) as eluent to give 3.09 g (46%) of the title compound as white solids. the reaction was stirred 1.5 hours at −78° C Reaction was quenched with NH4Cl (sat) (50 ml) and H2O (50 ml) to reach room temperature The aqueous phase was separated extracted with EtOAc (100 ml) The combined organics were washed with NH4Cl (sat) (2*100 ml), H2O (100 ml) dried over MgSO4 filtered evaporated was removed by precipitation from MeOH/H2O (9/1) The mother liquor was evaporated the residue purified by flash chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of the (4-bromobenzyloxy)-(tert.-butyl)-dimethylsilane (24.94 g, 82.8 mmol) in THF (420 mL) at −78° C. was added dropwise a 1.6 M solution of nBuLi in hexane (62 mL, 99.2 mmol) over a 1 h period. After stirring the mixture at the same temperature for 75 min, a solution of N,N-diethyltrifluoroacetamide (19.19 g, 113 nmol) in THF (60 mL) was added dropwise over 1 h. Following the addition the mixture at −78° C. for a further 75 min before the reaction was quenched with an aqueous solution of NH4Cl. Ether was added and the organic layer was extracted 3 times with ether (3×300 mL). The organic layers were combined, dried over Na2SO4 and concentrated in vacuum. The resulting pale yellow liquid was distillated in vacuo to give the 1-(4-((tert-butyldimethylsilyloxy)methyl)phenyl)-2,2,2-trifluoroethanone (65%) as a colorless liquid; b.p. 170-180° C. (10 torr), 1H NMR (CDCl3): δ 0.12 (s, (CH3)2Si), 0.96 (s, CH3)3C), 4.83 (s, CH2), 7.50 (d, J=8.2 Hz, C6H4), 8.05 (d, J=8.2 Hz, C6H4); 13C NMR (CDCl3): δ −5.4 (CH3Si), 18.3 (C(CH3)3), 25.8 (C(CH3)3), 64.2 (CH2O), 116.7 (q, J=289.7 Hz, CF3), 126.2 (C6H2), 128.6 (C6H2), 130.2 (C6H2), 150.1, (C6H2), 180.2 (q, J=34.5 Hz, CO). the addition the mixture at −78° C. for a further 75 min before the reaction was quenched with an aqueous solution of NH4Cl Ether was added the organic layer was extracted 3 times with ether (3×300 mL) dried over Na2SO4 concentrated in vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of the (4-bromobenzyloxy)-(tert.-butyl)-dimethylsilane (24.94 g, 82.8 mmol) in THF (420 mL) at −78° C. was added dropwise a 1.6 M solution of nBuLi in hexane (62 mL, 99.2 mmol) over a 1 h period. After stirring the mixture at the same temperature for 75 min, a solution of N,N-diethyltrifluoroacetamide (19.19 g, 113 nmol) in THF (60 mL) was added dropwise over 1 h. Following the addition the mixture at −78° C. for a further 75 min before the reaction was quenched with an aqueous solution of NH4Cl. Ether was added and the organic layer was extracted 3 times with ether (3×300 mL). The organic layers were combined, dried over Na2SO4 and concentrated in vacuum. The resulting pale yellow liquid was distillated in vacuo to give the 1-(4-((tert-butyldimethylsilyloxy)methyl)phenyl)-2,2,2-trifluoroethanone (65%) as a colorless liquid; b.p. 170-180° C. (10 torr), 1H NMR (CDCl3): δ 0.12 (s, (CH3)2Si), 0.96 (s, CH3)3C), 4.83 (s, CH2), 7.50 (d, J=8.2 Hz, C6H4), 8.05 (d, J=8.2 Hz, C6H4); 13C NMR (CDCl3): δ −5.4 (CH3Si), 18.3 (C(CH3)3), 25.8 (C(CH3)3), 64.2 (CH2O), 116.7 (q, J=289.7 Hz, CF3), 126.2 (C6H2), 128.6 (C6H2), 130.2 (C6H2), 150.1, (C6H2), 180.2 (q, J=34.5 Hz, CO). the addition the mixture at −78° C. for a further 75 min before the reaction was quenched with an aqueous solution of NH4Cl Ether was added the organic layer was extracted 3 times with ether (3×300 mL) dried over Na2SO4 concentrated in vacuum