2-butoxyacetic acid

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

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

Procedure: Sodium metal (16 g) was added to 92.5 ml of butanol and heated at reflux under nitrogen. After the sodium had reacted, chloroacetic acid (32.9 g) in 40 ml of butanol was added dropwise and then heated at reflux for twenty hours. The mixture, upon cooling to room temperature, was added to 1300 ml of water and extracted four times with 250-ml portions of diethyl ether. The aqueous phase was acidified to about pH 2 with aqueous hydrochloric acid and again extracted four times with 250-ml portions of diethyl ether. The organic extracts were combined and dried over sodium sulfate, filtered, and concentrated in vacuo. Distillation afforded the title compound as an oil. Structure assignment was supported by the proton nmr spectrum. heated at reflux under nitrogen heated at reflux for twenty hours extracted four times with 250-ml portions of diethyl ether again extracted four times with 250-ml portions of diethyl ether dried over sodium sulfate filtered concentrated in vacuo Distillation

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

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

Procedure: Following the procedure of Example 2, making variations only as required to use butoxyacetic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (40.8% yield). 1H NMR (300 MHz, CDCl3) δ 9.19, 8.35, 7.72, 7.55, 7.33, 7.03, 4.05, 3.94, 3.60, 3.31, 1.64, 1.43, 0.93. MS (ES+) m/z 465.6 (M+1).

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

Procedure: Following the procedure of Example 2, making variations only as required to use butoxyacetic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (40.8% yield). 1H NMR (300 MHz, CDCl3) δ 9.19, 8.35, 7.72, 7.55, 7.33, 7.03, 4.05, 3.94, 3.60, 3.31, 1.64, 1.43, 0.93. MS (ES+) m/z 465.6 (M+1).

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

Procedure: Following the procedure of Example 2, making variations only as required to use butoxyacetic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (40.8% yield). 1H NMR (300 MHz, CDCl3) δ 9.19, 8.35, 7.72, 7.55, 7.33, 7.03, 4.05, 3.94, 3.60, 3.31, 1.64, 1.43, 0.93. MS (ES+) m/z 465.6 (M+1).

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

Procedure: Following the procedure of Example 2, making variations only as required to use butoxyacetic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (40.8% yield). 1H NMR (300 MHz, CDCl3) δ 9.19, 8.35, 7.72, 7.55, 7.33, 7.03, 4.05, 3.94, 3.60, 3.31, 1.64, 1.43, 0.93. MS (ES+) m/z 465.6 (M+1).

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

Procedure: Following the procedure of Example 2, making variations only as required to use butoxyacetic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (40.8% yield). 1H NMR (300 MHz, CDCl3) δ 9.19, 8.35, 7.72, 7.55, 7.33, 7.03, 4.05, 3.94, 3.60, 3.31, 1.64, 1.43, 0.93. MS (ES+) m/z 465.6 (M+1).

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

Procedure: Following the procedure of Example 2, making variations only as required to use butoxyacetic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (40.8% yield). 1H NMR (300 MHz, CDCl3) δ 9.19, 8.35, 7.72, 7.55, 7.33, 7.03, 4.05, 3.94, 3.60, 3.31, 1.64, 1.43, 0.93. MS (ES+) m/z 465.6 (M+1).

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

Procedure: Following the procedure of Example 2, making variations only as required to use butoxyacetic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (40.8% yield). 1H NMR (300 MHz, CDCl3) δ 9.19, 8.35, 7.72, 7.55, 7.33, 7.03, 4.05, 3.94, 3.60, 3.31, 1.64, 1.43, 0.93. MS (ES+) m/z 465.6 (M+1).

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

Procedure: Methylene chloride (20 ml), 3-oxaheptanoic acid (529.0 mg, 4.0 mmol), triethylamine (1.40 ml, 10.0 mmol) and EDC (1.15 g, 6.0 mmol) were added to (1S,2S)-2-amino-3-morpholino-1-phenyl-1-propanol (944.0 mg, 4.0 mmol), followed by stirring overnight. Methylene chloride (100 ml) was added to the reaction solution. After washed with a saturated sodium hydrogen carbonate solution (50 ml), water (50 ml) and saturated brine (50 ml) successively, the organic layer was dried over sodium sulfate and filtered, and the solvent was evaporated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (chloroform:ethanol=30:1) to obtain the title compound (825 mg, yield 59%) as colorless oil. After washed with a saturated sodium hydrogen carbonate solution (50 ml), water (50 ml) and saturated brine (50 ml) successively the organic layer was dried over sodium sulfate filtered the solvent was evaporated under reduced pressure The resulting crude product was purified by silica gel column chromatography (chloroform:ethanol=30:1)

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

Procedure: Following the procedure of Example 2, making variations only as required to use butoxyacetic acid in place of benzyloxyacetic acid to react with [4-(6-aminopyridazin-3-yl)piperazin-1-yl](2-trifluoromethylphenyl)methanone, the title compound was obtained as a white powder (40.8% yield). 1H NMR (300 MHz, CDCl3) δ 9.19, 8.35, 7.72, 7.55, 7.33, 7.03, 4.05, 3.94, 3.60, 3.31, 1.64, 1.43, 0.93. MS (ES+) m/z 465.6 (M+1).