5-fluoro-2-(2,2,2-trifluoroethoxy)aniline

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

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

Conditions: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.66 g of Compound 5A and 0.07 g of Raney-Nickel in 20 mL of ethyl acetate was stirred for 14 hours at 20-25° C. The organic layer was separated and the mixture extracted with 2×40 mL of ethyl acetate. The combined organic layers were washed with 20 mL of brine, dried over sodium sulphate and evaporated to dryness in vacuo to afford 0.52 g (90.6%) of Compound 5B as an orange oil. The organic layer was separated the mixture extracted with 2×40 mL of ethyl acetate The combined organic layers were washed with 20 mL of brine dried over sodium sulphate evaporated to dryness in vacuo

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

Procedure: A stirred mixture of 0.52 g of Compound 8B, 0.45 g of 98% bis-(2-chloroethyl)amine hydrochloride, 0.5 g of potassium iodide, 0.34 g of anhydrous potassium carbonate and 20 mL of n-butanol was refluxed for 32 hours under nitrogen. The solvent was removed under reduced pressure; the residue was treated with 10 mL of water and 10 mL of 20% aqueous sodium carbonate and extracted with 2×30 mL of ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and evaporated to dryness in vacuo. The residue was purified by flash chromatography (chloroform/2N ammonia solution in methanol, gradient from 100:3to 100:5) to afford 0.1 g (14%) of Compound 8C as an oil. was refluxed for 32 hours under nitrogen The solvent was removed under reduced pressure the residue was treated with 10 mL of water and 10 mL of 20% aqueous sodium carbonate extracted with 2×30 mL of ethyl acetate The organic layer was washed with brine dried over sodium sulphate evaporated to dryness in vacuo The residue was purified by flash chromatography (chloroform/2N ammonia solution in methanol, gradient from 100:3to 100:5)

Conditions: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.66 g of Compound 8A and 0.07 g of Raney-Nickel in 20 mL of ethyl acetate was stirred for 14 hours at 20-25° C. The catalyst was filtered off. The mixture was diluted with water. The organic layer was separated and the mixture extracted with 2×40 mL of ethyl acetate. The combined organic layers were washed with 20 mL of brine, dried over sodium sulphate and evaporated to dryness in vacuo to afford 0.52 g (90.6%) of Compound 8B as an oil. The catalyst was filtered off The mixture was diluted with water The organic layer was separated the mixture extracted with 2×40 mL of ethyl acetate The combined organic layers were washed with 20 mL of brine dried over sodium sulphate evaporated to dryness in vacuo

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

Procedure: A stirred mixture of 0.52 g of Compound 5B, 0.45 g of bis-(2-chloroethyl)amine hydrochloride, 0.5 g of potassium iodide, 0.34 g of anhydrous potassium carbonate and 20 mL of n-butanol was refluxed for 32 hours under nitrogen. The solvent was removed under reduced pressure. The residue was treated with 10 mL of water and 10 mL of 20% aqueous sodium carbonate and extracted with 2×30 mL of ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and evaporated to dryness in vacuo. The residue was purified by flash chromatography (chloroform:2N ammonia in methanol gradient from 100:3 to 100:5) to afford 0.1 g (14%) of Compound 5C as an oil. was refluxed for 32 hours under nitrogen The solvent was removed under reduced pressure The residue was treated with 10 mL of water and 10 mL of 20% aqueous sodium carbonate extracted with 2×30 mL of ethyl acetate The organic layer was washed with brine dried over sodium sulphate evaporated to dryness in vacuo The residue was purified by flash chromatography (chloroform:2N ammonia in methanol gradient from 100:3 to 100:5)

Conditions: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.66 g of Compound 5A and 0.07 g of Raney-Nickel in 20 mL of ethyl acetate was stirred for 14 hours at 20-25° C. The organic layer was separated and the mixture extracted with 2×40 mL of ethyl acetate. The combined organic layers were washed with 20 mL of brine, dried over sodium sulphate and evaporated to dryness in vacuo to afford 0.52 g (90.6%) of Compound 5B as an orange oil. The organic layer was separated the mixture extracted with 2×40 mL of ethyl acetate The combined organic layers were washed with 20 mL of brine dried over sodium sulphate evaporated to dryness in vacuo

Conditions: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.66 g of Compound 5A and 0.07 g of Raney-Nickel in 20 mL of ethyl acetate was stirred for 14 hours at 20-25° C. The organic layer was separated and the mixture extracted with 2×40 mL of ethyl acetate. The combined organic layers were washed with 20 mL of brine, dried over sodium sulphate and evaporated to dryness in vacuo to afford 0.52 g (90.6%) of Compound 5B as an orange oil. The organic layer was separated the mixture extracted with 2×40 mL of ethyl acetate The combined organic layers were washed with 20 mL of brine dried over sodium sulphate evaporated to dryness in vacuo