N-[2-(4-bromophenyl)ethyl]-2,2,2-trifluoroacetamide

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 stirred solution of 23.89 g of N-[2-(4-bromophenyl)ethyl]-2,2,2-trifluoroacetamide in 200 mL of acetonitrile was added in one portion 13.87 g of nitronium tetrafluoroborate under ice-cooling. After the mixture was stirred at room temperature for 15 minutes, to the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: ethyl acetate-hexane) to give 11.03 g of N-[2-(4-bromo-2-nitrophenyl)ethyl]-2,2,2-trifluoroacetamide. cooling the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: ethyl acetate-hexane)

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(4-bromophenethyl)-2,2,2-trifluoroacetamide (2.96 g, 10 mmol), NiBr2 (2.19 g, 10 mmol) and NaCN (0.98 g, 20 mmol) in 2.0 mL of NMP was heated at 200° C. in microwave twice. After cooling down to RT, the mixture was filtered with the help excess of DCM. The filtrate was evaporated to dryness and was submitted to flash chomatography (SiO2, DCM to DCM/EtOAc=3:1) to give (N-(4-cyanophenethyl)-2,2,2-trifluoroacetamide was a white solid, together with 1.1 g for recovered starting material. After cooling down to RT the mixture was filtered with the help excess of DCM The filtrate was evaporated to dryness

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

Procedure: To a suspension of N-(4-bromophenethyl)-2,2,2-trifluoroacetamide (8.88 g, 30 mmol) and paraformaldehyde (13.5 g, 0.45 mol) in 45 mL of glacial acetic acid at room temperature was slowly added 30 mL of sulfuric acid (96.6%). After stirring at room temperature overnight, the reaction mixture was quenched with ice water and extracted with EtOAc, washed with brine and Sat. NaHCO3 and dried over Na2SO4. After concentration, flash chomatography (SiO2, hexane/DCM=1:1) gave 1-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethanone as a white solid. the reaction mixture was quenched with ice water extracted with EtOAc washed with brine and Sat. NaHCO3 dried over Na2SO4 After concentration, flash chomatography (SiO2, hexane/DCM=1:1)

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

Procedure: Concentrated sulfuric acid (35 mL) was added to glacial acetic acid (45mL) with stirring and ice-cooling. After stirring for 30 minutes the mixture was treated with N-2-(4-bromophenyl)ethyl trifluoroacetamide (10.4 g, Reference Example 8) and then with paraformaldehyde (1.75 g). This mixture was allowed to warm to room temperature and after stirring for a further 24 hours the pale brown solution was treated with a further aliquat of paraformaldehyde (0.8 g). After stirring for a further 24 hours the reaction mixture was treated with iced-water (500 mL) and then extracted three times with ethyl acetate (200 mL). The combined extracts were washed twice with water (200 mL), then four times with aqueous sodium bicarbonate solution (200 mL), then twice with water (200 mL), then dried over magnesium sulfate and then evaporated. The residual yellow oil was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (3:97, v/v) to give the title compound as a white crystalline solid. LC-MS: RT=4.76 minutes; no molecular ion observed. ice-cooling After stirring for 30 minutes the mixture after stirring for a further 24 hours the pale brown solution After stirring for a further 24 hours the reaction mixture extracted three times with ethyl acetate (200 mL) The combined extracts were washed twice with water (200 mL) four times with aqueous sodium bicarbonate solution (200 mL), then twice with water (200 mL), then dried over magnesium sulfate evaporated The residual yellow oil was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (3:97

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

Procedure: Into acetic acid (42 ml) were added dropwise under ice cooling sulfuric acid (28 ml), subsequently N-(2-(4-bromophenyl)ethyl)trifluoroacetamide (7.8 g) and paraformamide (1.27 g) and the resulting mixture was stirred overnight under a nitrogen atmosphere. The reaction mixture was poured into ice water and was extracted with ethyl acetate. The organic layer was washed with an aqueous solution of sodium hydrogen carbonate, water and an aqueous saturated solution of sodium chloride, and was then dried with anhydrous magnesium sulfate. The resulting organic layer was evaporated under reduced pressure to remove the solvent to obtain 7-bromo-2-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline (8.1 g) as a colorless oil. was extracted with ethyl acetate The organic layer was washed with an aqueous solution of sodium hydrogen carbonate, water an aqueous saturated solution of sodium chloride, and was then dried with anhydrous magnesium sulfate The resulting organic layer was evaporated under reduced pressure to remove the solvent

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