2-(4-fluorophenoxy)-2-methylpropan-1-amine

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 mixture of 4-amino-3-fluorobenzoic acid (200.0 mg, 1.289 mmol) and HBTU (490 mg, 1.3 mmol) in DMF (2 mL, 20 mmol) at 0° C. were added N,N-diisopropylethylamine (0.67 mL, 3.9 mmol) and 2-(4-fluorophenoxy)-2-methylpropan-1-amine (Preparation 91, 280 mg, 1.5 mmol). The reaction mixture was slowly warmed to ambient temperature. The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic layers were washed successively with water, aqueous lithium chloride, and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform). The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate extracted with ethyl acetate (3×) The combined organic layers were washed successively with water, aqueous lithium chloride, and brine dried over sodium sulfate filtered concentrated in vacuo The residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 1 L-single neck round-bottom flask was added 2-(4-fluorophenoxy)-2-methylpropanoic acid (5.10 g, 0.0257 mol), methylene chloride (66.0 mL, 1.03 mol), oxalyl chloride (3.27 mL, 0.0386 mol) and N,N-dimethylformamide (20 μL, 0.0003 mol). The reaction was stirred until bubbling had stopped. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Borane-dimethyl sulfide complex (5.7 mL, 0.064 mol) was added to the amide in THF (50 mL, 0.6 mol) at room temperature. The reaction was heated at 65° C. overnight. MeOH was added carefully. 1 N HCl was added and was heated at 65° C. for 2 hours. The reaction was concentrated in vacuo. The solid was dissolved in water and was washed with DCM. The aq. layer was basified with 1 N NaOH. The reaction was extracted with DCM. The reaction was dried with MgSO4 and concentrated in vacuo to afford the title compound. until bubbling Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added was heated at 65° C. for 2 hours The reaction was concentrated in vacuo The solid was dissolved in water was washed with DCM The reaction was extracted with DCM The reaction was dried with MgSO4 concentrated in vacuo

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

Procedure: To a mixture of 4-amino-3-fluorobenzoic acid (200.0 mg, 1.289 mmol) and HBTU (490 mg, 1.3 mmol) in DMF (2 mL, 20 mmol) at 0° C. were added N,N-diisopropylethylamine (0.67 mL, 3.9 mmol) and 2-(4-fluorophenoxy)-2-methylpropan-1-amine (Preparation 91, 280 mg, 1.5 mmol). The reaction mixture was slowly warmed to ambient temperature. The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic layers were washed successively with water, aqueous lithium chloride, and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform). The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate extracted with ethyl acetate (3×) The combined organic layers were washed successively with water, aqueous lithium chloride, and brine dried over sodium sulfate filtered concentrated in vacuo The residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 1 L-single neck round-bottom flask was added 2-(4-fluorophenoxy)-2-methylpropanoic acid (5.10 g, 0.0257 mol), methylene chloride (66.0 mL, 1.03 mol), oxalyl chloride (3.27 mL, 0.0386 mol) and N,N-dimethylformamide (20 μL, 0.0003 mol). The reaction was stirred until bubbling had stopped. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Borane-dimethyl sulfide complex (5.7 mL, 0.064 mol) was added to the amide in THF (50 mL, 0.6 mol) at room temperature. The reaction was heated at 65° C. overnight. MeOH was added carefully. 1 N HCl was added and was heated at 65° C. for 2 hours. The reaction was concentrated in vacuo. The solid was dissolved in water and was washed with DCM. The aq. layer was basified with 1 N NaOH. The reaction was extracted with DCM. The reaction was dried with MgSO4 and concentrated in vacuo to afford the title compound. until bubbling Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added was heated at 65° C. for 2 hours The reaction was concentrated in vacuo The solid was dissolved in water was washed with DCM The reaction was extracted with DCM The reaction was dried with MgSO4 concentrated in vacuo

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 1 L-single neck round-bottom flask was added 2-(4-fluorophenoxy)-2-methylpropanoic acid (5.10 g, 0.0257 mol), methylene chloride (66.0 mL, 1.03 mol), oxalyl chloride (3.27 mL, 0.0386 mol) and N,N-dimethylformamide (20 μL, 0.0003 mol). The reaction was stirred until bubbling had stopped. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Borane-dimethyl sulfide complex (5.7 mL, 0.064 mol) was added to the amide in THF (50 mL, 0.6 mol) at room temperature. The reaction was heated at 65° C. overnight. MeOH was added carefully. 1 N HCl was added and was heated at 65° C. for 2 hours. The reaction was concentrated in vacuo. The solid was dissolved in water and was washed with DCM. The aq. layer was basified with 1 N NaOH. The reaction was extracted with DCM. The reaction was dried with MgSO4 and concentrated in vacuo to afford the title compound. until bubbling Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added was heated at 65° C. for 2 hours The reaction was concentrated in vacuo The solid was dissolved in water was washed with DCM The reaction was extracted with DCM The reaction was dried with MgSO4 concentrated in vacuo

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

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

Procedure: To a mixture of 4-amino-3-fluorobenzoic acid (200.0 mg, 1.289 mmol) and HBTU (490 mg, 1.3 mmol) in DMF (2 mL, 20 mmol) at 0° C. were added N,N-diisopropylethylamine (0.67 mL, 3.9 mmol) and 2-(4-fluorophenoxy)-2-methylpropan-1-amine (Preparation 91, 280 mg, 1.5 mmol). The reaction mixture was slowly warmed to ambient temperature. The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic layers were washed successively with water, aqueous lithium chloride, and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform). The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate extracted with ethyl acetate (3×) The combined organic layers were washed successively with water, aqueous lithium chloride, and brine dried over sodium sulfate filtered concentrated in vacuo The residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 1 L-single neck round-bottom flask was added 2-(4-fluorophenoxy)-2-methylpropanoic acid (5.10 g, 0.0257 mol), methylene chloride (66.0 mL, 1.03 mol), oxalyl chloride (3.27 mL, 0.0386 mol) and N,N-dimethylformamide (20 μL, 0.0003 mol). The reaction was stirred until bubbling had stopped. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Borane-dimethyl sulfide complex (5.7 mL, 0.064 mol) was added to the amide in THF (50 mL, 0.6 mol) at room temperature. The reaction was heated at 65° C. overnight. MeOH was added carefully. 1 N HCl was added and was heated at 65° C. for 2 hours. The reaction was concentrated in vacuo. The solid was dissolved in water and was washed with DCM. The aq. layer was basified with 1 N NaOH. The reaction was extracted with DCM. The reaction was dried with MgSO4 and concentrated in vacuo to afford the title compound. until bubbling Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added was heated at 65° C. for 2 hours The reaction was concentrated in vacuo The solid was dissolved in water was washed with DCM The reaction was extracted with DCM The reaction was dried with MgSO4 concentrated in vacuo

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

Procedure: To a mixture of 4-amino-3-fluorobenzoic acid (200.0 mg, 1.289 mmol) and HBTU (490 mg, 1.3 mmol) in DMF (2 mL, 20 mmol) at 0° C. were added N,N-diisopropylethylamine (0.67 mL, 3.9 mmol) and 2-(4-fluorophenoxy)-2-methylpropan-1-amine (Preparation 91, 280 mg, 1.5 mmol). The reaction mixture was slowly warmed to ambient temperature. The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic layers were washed successively with water, aqueous lithium chloride, and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform). The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate extracted with ethyl acetate (3×) The combined organic layers were washed successively with water, aqueous lithium chloride, and brine dried over sodium sulfate filtered concentrated in vacuo The residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 1 L-single neck round-bottom flask was added 2-(4-fluorophenoxy)-2-methylpropanoic acid (5.10 g, 0.0257 mol), methylene chloride (66.0 mL, 1.03 mol), oxalyl chloride (3.27 mL, 0.0386 mol) and N,N-dimethylformamide (20 μL, 0.0003 mol). The reaction was stirred until bubbling had stopped. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Volatiles were removed and crude product then dissolved in DCM and 15 mL of 7N ammonia in MeOH was added. Borane-dimethyl sulfide complex (5.7 mL, 0.064 mol) was added to the amide in THF (50 mL, 0.6 mol) at room temperature. The reaction was heated at 65° C. overnight. MeOH was added carefully. 1 N HCl was added and was heated at 65° C. for 2 hours. The reaction was concentrated in vacuo. The solid was dissolved in water and was washed with DCM. The aq. layer was basified with 1 N NaOH. The reaction was extracted with DCM. The reaction was dried with MgSO4 and concentrated in vacuo to afford the title compound. until bubbling Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added Volatiles were removed crude product then dissolved in DCM 15 mL of 7N ammonia in MeOH was added was heated at 65° C. for 2 hours The reaction was concentrated in vacuo The solid was dissolved in water was washed with DCM The reaction was extracted with DCM The reaction was dried with MgSO4 concentrated in vacuo