(1E)-N-hydroxy-2-phenylethanimidoyl chloride

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

Procedure: Synthesised as with 4-(3-phenyl-5-isoxazolyl)-1-butanol, using N-hydroxy-2-phenylethanimidoyl chloride (253 mg, 1.5 mmol) and 4-pentyn-1-ol (139 mg, 1.65 mmol). Yield 61 mg of pale yellow oil.

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylacetaldehyde oxime (40.5 g, 300 mmol) was dissolved in acetonitrile (100 ml). To the solution, a 6.7% aqueous hydrochloric acid (145 g) and then an 8.5% so aqueous sodium hypochlorite (262 g, 299 mmol) were added dropwise at -10° C. over 2.3 hours. The mixture was stirred at -5° C. for 30 minutes and then combined with toluene (200 ml) for extraction. The separated organic layer was washed twice with water (200 ml). Reversed phase HPLC revealed that the extract contained 40.3 g (238 mmol, yield 79%) of the desired compound. The solution was used in the next step without concentration. combined with toluene (200 ml) for extraction The separated organic layer was washed twice with water (200 ml)

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylacetaldehyde oxime (40.5 g, 300 mmol) was dissolved in acetonitrile (100 ml). To the solution, a 6.7% aqueous hydrochloric acid (145 g) and then an 8.5% aqueous sodium hypochlorite (262 g, 299 mmol) were added dropwise at -10° C. over 2.3 hours. The mixture was stirred at -5° C. for 30 minutes and then combined with toluene (200 ml) for extraction. The separated organic layer was washed twice with water (200 ml). Reversed phase HPLC revealed that the extract contained 40.3 g (238 mmol, yield 79%) of the desired compound. The solution was used in the next step without concentration. combined with toluene (200 ml) for extraction The separated organic layer was washed twice with water (200 ml)

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

Procedure: Compound W (3.33 g, 20 mmol), dissolved in abs. DCM (15 ml), was added dropwise at 0° C. within 10 min to a solution of compound B (2.81 g, 14.3 mmol in abs. DCM (22 ml)). A solution of triethylamine (11.2 ml, 80 mmol) in abs. DCM (10 ml) was added to this mixture at 0° C. within 10 min. As the reaction was highly exothermic, cooling was carried out with a mixture of ice and sodium chloride. The reaction mixture was stirred for 16 h at RT. For working up the mixture, DCM (15 ml) and water (45 ml) were added and the mixture was stirred for 15 min. After separation of the phases, the aqueous phase was extracted with DCM (2×45 ml). The phases were separated. The organic phase was washed successively with 10% citric acid solution (2×30 ml) and sat. NaCl solution (30 ml). The organic phase was dried and concentrated (5.3 g, brown oil). The residue was separated by chromatography [silica gel 60 (180 g); cyclohexane/EtOAc 7:1 (1,200 ml); 5:1 (900 ml)]. The desired product X was obtained in a yield of 681 mg (11%). cooling were added the mixture was stirred for 15 min After separation of the phases the aqueous phase was extracted with DCM (2×45 ml) The phases were separated The organic phase was washed successively with 10% citric acid solution (2×30 ml) and sat. NaCl solution (30 ml) The organic phase was dried concentrated (5.3 g, brown oil) The residue was separated by chromatography [silica gel 60 (180 g); cyclohexane/EtOAc 7:1 (1,200 ml); 5:1 (900 ml)]

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

Procedure: A solution of N-chlorosuccinimide (3.25 g, 24 mmol) in abs. DMF (18 ml) was added to a solution of compound V (2.7 g, 20 mmol) in abs. DMF (12 ml) at a temperature of 30-40° C. within 20 min. Cooling in an ice bath was carried out if necessary. The reaction mixture was stirred for 3 h at RT and then mixed with diethyl ether (175 ml) and water (115 ml). The phases were separated and the aqueous phase was extracted with diethyl ether (2×75 ml). The combined organic extracts were washed successively with water (100 ml) and sat. NaCl solution (100 ml). The organic phase was dried and concentrated. Compound W was obtained as a yellowish-green oil (3.33 g) and immediately reacted further. Cooling in an ice bath The phases were separated the aqueous phase was extracted with diethyl ether (2×75 ml) The combined organic extracts were washed successively with water (100 ml) and sat. NaCl solution (100 ml) The organic phase was dried concentrated

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylacetaldehyde oxime (40.5 g, 300 mmol) was dissolved in acetonitrile (100 ml). To the solution, a 6.7% aqueous hydrochloric acid (145 g) and then an 8.5% aqueous sodium hypochlorite (262 g, 299 mmol) were added dropwise at -10° C. over 2.3 hours. The mixture was stirred at -5° C. for 30 minutes and then combined with toluene (200 ml) for extraction. The separated organic layer was washed twice with water (200 ml). Reversed phase HPLC revealed that the extract contained 40.3 g (238 mmol, yield 79%) of the desired compound. The solution was used in the next step without concentration. combined with toluene (200 ml) for extraction The separated organic layer was washed twice with water (200 ml)

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylacetaldehyde oxime (40.5 g, 300 mmol) was dissolved in acetonitrile (100 ml). To the solution, a 6.7% aqueous hydrochloric acid (145 g) and then an 8.5% aqueous sodium hypochlorite (262 g, 299 mmol) were added dropwise at -10° C. over 2.3 hours. The mixture was stirred at -5° C. for 30 minutes and then combined with toluene (200 ml) for extraction. The separated organic layer was washed twice with water (200 ml). Reversed phase HPLC revealed that the extract contained 40.3 g (238 mmol, yield 79%) of the desired compound. The solution was used in the next step without concentration. combined with toluene (200 ml) for extraction The separated organic layer was washed twice with water (200 ml)

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

Procedure: Synthesised as with 4-(3-phenyl-5-isoxazolyl)-1-butanol, using N-hydroxy-2-phenylethanimidoyl chloride (253 mg, 1.5 mmol) and 4-pentyn-1-ol (139 mg, 1.65 mmol). Yield 61 mg of pale yellow oil.

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylacetaldehyde oxime (40.5 g, 300 mmol) was dissolved in acetonitrile (100 ml). To the solution, a 6.7% aqueous hydrochloric acid (145 g) and then an 8.5% so aqueous sodium hypochlorite (262 g, 299 mmol) were added dropwise at -10° C. over 2.3 hours. The mixture was stirred at -5° C. for 30 minutes and then combined with toluene (200 ml) for extraction. The separated organic layer was washed twice with water (200 ml). Reversed phase HPLC revealed that the extract contained 40.3 g (238 mmol, yield 79%) of the desired compound. The solution was used in the next step without concentration. combined with toluene (200 ml) for extraction The separated organic layer was washed twice with water (200 ml)