1-azido-4-fluorobenzene

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: Prepared in analogy to EP 0 433 842 A2. A mixture of 1-azido-4-fluoro-benzene (2.80 g, 20 mmol) and 1-(1-propenyl)-piperidine (18%, 14.2 g, 20 mmol) was stirred under ice cooling (slowly exothermic in the beginning) and at room temperature for 144 h in the absence of light. Hexane was then added to the brown solutions and a solid formed which was filtered off, washed with hexane and dried in hv to give the title product (1.1 g) as a light pink solid. The filtrate was then evaporated and purification by chromatography (silica, 10 to 50% ethyl acetate in heptane) afforded the title compound (4.34 g) as a light yellow solid. Total yield (5.44 g, 98%). MS: m/e=263.1 [M+H]+. a solid formed which was filtered off washed with hexane dried in hv

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

Procedure: Prepared in analogy to J. Org. Chem. (1989) 54:5938-5945. To a solution of sulfuric acid (40 mL) and trifluoroacetic acid (200 mL) was added 4-fluoroaniline (22.1 mL, 0.23 mol) dropwise. Then under ice-cooling a solution of sodium nitrite (20.6 g, 0.3 mol) in water (200 mL) was added over 30 min at 15-18° C. The solution was then stirred for 30 min while kept in the ice bath. A solution of sodium azide (25.42 g, 0.39 mol) in water (150 mL) was added dropwise over 30 min. Mixture was foaming and temperature went up to 10° C. while cooling with an ice bath. Reaction mixture was stirred without cooling for 1 h, then extracted with diethyl ether. The combined organic layers were washed with water two times. Then the combined organic layers were diluted with saturated aqueous sodium carbonate solution (500 mL) until the mixture became basic. The organic phase was separated and washed with brine, extracted again with diethyl ether. The organic layers were dried over sodium sulfate and evaporated at 40° C., minimum 50 mbar (already distillation of product), to afford the title product (30.42 g, 96%) as a brown liquid. Prepared in analogy to J was added over 30 min at 15-18° C went up to 10° C. while cooling with an ice bath Reaction mixture was stirred without cooling for 1 h extracted with diethyl ether The combined organic layers were washed with water two times Then the combined organic layers were diluted with saturated aqueous sodium carbonate solution (500 mL) until the mixture The organic phase was separated washed with brine extracted again with diethyl ether The organic layers were dried over sodium sulfate evaporated at 40° C. minimum 50 mbar (already distillation of product),

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

Procedure: 1-(1-propenyl)-piperidine (9.4 g; 75.07 mmol) and 4-fluorophenylazide (10.3 g; 75.07 mmol), prepared as described in example 1, were admixed at 0° C. and the resultant mixture was kept at room temperature for 54 hours in the absence of light. The obtained solid mass was collected with petroleum ether and filtered obtaining the title compound (6 g). The mother liquor was evaporated and the resultant crude compound was purified by chromatography on silica gel (230-400 mesh), eluent petroleum ether:ethyl acetate=9:1, obtaining further title compound (m.p. 75° 76° C.). were admixed at 0° C. The obtained solid mass was collected with petroleum ether filtered

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

Procedure: 1-(1-propenyl)-piperidine (9.4 g; 75.07 mmol) and 4-fluorophenylazide (10.3 g; 75.07 mmol), prepared as described in example 1, were admixed at 0° C. and the resultant mixture was kept at room temperature for 54 hours in the absence of light. The obtained solid mass was collected with petroleum ether and filtered obtaining the title compound (6 g). The mother liquor was evaporated and the resultant crude compound was purified by chromatography on silica gel (230-400 mesh), eluent petroleum ether:ethyl acetate=9:1, obtaining further title compound (m.p. 75° 76° C.). were admixed at 0° C. The obtained solid mass was collected with petroleum ether filtered

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

Procedure: 1-Azido-4-fluorobenzene (24 mg, 0.174 mmol) was dissolved in N,N-diisopropylethylamine (0.75 ml), then (S)-tert-butyl 2-(4-ethynylphenyl)morpholine-4-carboxylate (50 mg, 0.175 mmol) was added followed by copper(I) iodide (33 mg, 0.174 mmol). The mixture was stirred at room temperature for 3 h. The green mixture was concentrated on the rotavap, silica gel (0.5 g) was added and after short grinding the mixture was put on a silica gel column for purification. Flash chromatography (5 g silica gel, 30% ethyl acetate in heptane) yielded a white solid (21 mg, 28%). MS (ISP): 369.1 ([M-tBu+H]+), 425.2 ([M+H]+). The green mixture was concentrated on the rotavap, silica gel (0.5 g) was added after short grinding the mixture was put on a silica gel column for purification

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

Procedure: 1-Azido-4-fluorobenzene (24 mg, 0.174 mmol) was dissolved in N,N-diisopropylethylamine (0.75 ml), then (S)-tert-butyl 2-(4-ethynylphenyl)morpholine-4-carboxylate (50 mg, 0.175 mmol) was added followed by copper(I) iodide (33 mg, 0.174 mmol). The mixture was stirred at room temperature for 3 h. The green mixture was concentrated on the rotavap, silica gel (0.5 g) was added and after short grinding the mixture was put on a silica gel column for purification. Flash chromatography (5 g silica gel, 30% ethyl acetate in heptane) yielded a white solid (21 mg, 28%). MS (ISP): 369.1 ([M-tBu+H]+), 425.2 ([M+H]+). The green mixture was concentrated on the rotavap, silica gel (0.5 g) was added after short grinding the mixture was put on a silica gel column for purification

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

Procedure: Prepared in analogy to EP 0 433 842 A2. A mixture of 1-azido-4-fluoro-benzene (2.80 g, 20 mmol) and 1-(1-propenyl)-piperidine (18%, 14.2 g, 20 mmol) was stirred under ice cooling (slowly exothermic in the beginning) and at room temperature for 144 h in the absence of light. Hexane was then added to the brown solutions and a solid formed which was filtered off, washed with hexane and dried in hv to give the title product (1.1 g) as a light pink solid. The filtrate was then evaporated and purification by chromatography (silica, 10 to 50% ethyl acetate in heptane) afforded the title compound (4.34 g) as a light yellow solid. Total yield (5.44 g, 98%). MS: m/e=263.1 [M+H]+. a solid formed which was filtered off washed with hexane dried in hv

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

Procedure: Prepared in analogy to EP 0 433 842 A2. A mixture of 1-azido-4-fluoro-benzene (2.80 g, 20 mmol) and 1-(1-propenyl)-piperidine (18%, 14.2 g, 20 mmol) was stirred under ice cooling (slowly exothermic in the beginning) and at room temperature for 144 h in the absence of light. Hexane was then added to the brown solutions and a solid formed which was filtered off, washed with hexane and dried in hv to give the title product (1.1 g) as a light pink solid. The filtrate was then evaporated and purification by chromatography (silica, 10 to 50% ethyl acetate in heptane) afforded the title compound (4.34 g) as a light yellow solid. Total yield (5.44 g, 98%). MS: m/e=263.1 [M+H]+. a solid formed which was filtered off washed with hexane dried in hv

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

Procedure: Prepared in analogy to J. Org. Chem. (1989) 54:5938-5945. To a solution of sulfuric acid (40 mL) and trifluoroacetic acid (200 mL) was added 4-fluoroaniline (22.1 mL, 0.23 mol) dropwise. Then under ice-cooling a solution of sodium nitrite (20.6 g, 0.3 mol) in water (200 mL) was added over 30 min at 15-18° C. The solution was then stirred for 30 min while kept in the ice bath. A solution of sodium azide (25.42 g, 0.39 mol) in water (150 mL) was added dropwise over 30 min. Mixture was foaming and temperature went up to 10° C. while cooling with an ice bath. Reaction mixture was stirred without cooling for 1 h, then extracted with diethyl ether. The combined organic layers were washed with water two times. Then the combined organic layers were diluted with saturated aqueous sodium carbonate solution (500 mL) until the mixture became basic. The organic phase was separated and washed with brine, extracted again with diethyl ether. The organic layers were dried over sodium sulfate and evaporated at 40° C., minimum 50 mbar (already distillation of product), to afford the title product (30.42 g, 96%) as a brown liquid. Prepared in analogy to J was added over 30 min at 15-18° C went up to 10° C. while cooling with an ice bath Reaction mixture was stirred without cooling for 1 h extracted with diethyl ether The combined organic layers were washed with water two times Then the combined organic layers were diluted with saturated aqueous sodium carbonate solution (500 mL) until the mixture The organic phase was separated washed with brine extracted again with diethyl ether The organic layers were dried over sodium sulfate evaporated at 40° C. minimum 50 mbar (already distillation of product),