1,3-dibromopropan-2-yloxymethylbenzene

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11 parts of 2-benzyloxy-1,3-dibromo-propane, 30 parts of iso-propylamine and 30 parts of water were added to a stainless autoclave, and the mixture was heated at 80° C. for 2 hours with agitation. The reaction mixture was cooled and treted in the same manner as in Example 29, followed by distillation under reduced pressure. As a result 18 parts of 3-benzyloxy-1-(iso-propyl)azetidine boiling at 104° - 107° C. under 2 mm Hg were obtained The reaction mixture was cooled followed by distillation under reduced pressure

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methylsulfinyl(methylthio)methane (13 ml, 125 mmol) was dissolved in 250 ml THF and cooled to −20° C. n-Butyllithium (50 ml, 125 mmol) was added and the mixture was stirred for 3 h at −20° C. The mixture was cooled down to −78° C. and a solution of 1-((1,3-dibromopropan-2-yloxy)methyl)benzene (16.000 g, 52 mmol) was added. The reaction was stirred over night and allowed to warm up to RT. It was stirred for an additional 6 h at RT, hydrolyzed with water and extracted with EtOAc. The combined organic extracts were evaporated, dissolved in ether (50 ml) and treated with conc. HCl (10 ml) for 30 min at reflux. The mixture was neutralized with NaOH (10M) and extracted with EtOAc. The combined organic extracts were dried over MgSO4 and evaporated. Glass col. Chrom. (10-50% EtOAc in Hex) gave 3-(benzyloxy)cyclobutanone as a yellow oil. was added The mixture was cooled down to −78° C. The reaction was stirred over night to warm up to RT extracted with EtOAc The combined organic extracts were evaporated dissolved in ether (50 ml) treated with conc. HCl (10 ml) for 30 min at reflux extracted with EtOAc The combined organic extracts were dried over MgSO4 evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11 parts of 2-benzyloxy-1,3-dibromo-propane, 30 parts of iso-propylamine and 30 parts of water were added to a stainless autoclave, and the mixture was heated at 80° C. for 2 hours with agitation. The reaction mixture was cooled and treted in the same manner as in Example 29, followed by distillation under reduced pressure. As a result 18 parts of 3-benzyloxy-1-(iso-propyl)azetidine boiling at 104° - 107° C. under 2 mm Hg were obtained The reaction mixture was cooled followed by distillation under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11 parts of 2-benzyloxy-1,3-dibromo-propane, 30 parts of iso-propylamine and 30 parts of water were added to a stainless autoclave, and the mixture was heated at 80° C. for 2 hours with agitation. The reaction mixture was cooled and treted in the same manner as in Example 29, followed by distillation under reduced pressure. As a result 18 parts of 3-benzyloxy-1-(iso-propyl)azetidine boiling at 104° - 107° C. under 2 mm Hg were obtained The reaction mixture was cooled followed by distillation under reduced pressure

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(Benzyloxy)cyclobutanone Methylsulfinyl(methylthio)methane (13 ml, 125 mmol) was dissolved in 250 ml THF and cooled to −20° C. n-Butyllithium (50 ml, 125 mmol) was added and the mixture was stirred for 3 h at −20° C. The mixture was cooled down to −78° C. and a solution of 1-((1,3-dibromopropan-2-yloxy)methyl)benzene (16.000 g, 52 mmol) was added. The reaction was stirred over night and allowed to warm up to RT. It was stirred for an additional 6h at RT, hydrolyzed with water and extracted with EtOAc. The combined organic extracts were evaporated, dissolved in ether (50 ml) and treated with conc. HCl (10 ml) for 30 min at reflux. The mixture was neutralized with NaOH (10M) and extracted with EtOAc. The combined organic extracts were dried over MgSO4 and evaporated. Glass col. Chrom. (10-50% EtOAc in Hex) gave 3-(benzyloxy)cyclobutanone as a yellow oil. was added The mixture was cooled down to −78° C. The reaction was stirred over night to warm up to RT extracted with EtOAc The combined organic extracts were evaporated dissolved in ether (50 ml) treated with conc. HCl (10 ml) for 30 min at reflux extracted with EtOAc The combined organic extracts were dried over MgSO4 evaporated

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

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

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(Benzyloxy)cyclobutanone Methylsulfinyl(methylthio)methane (13 ml, 125 mmol) was dissolved in 250 ml THF and cooled to −20° C. n-Butyllithium (50 ml, 125 mmol) was added and the mixture was stirred for 3 h at −20° C. The mixture was cooled down to −78° C. and a solution of 1-((1,3-dibromopropan-2-yloxy)methyl)benzene (16.000 g, 52 mmol) was added. The reaction was stirred over night and allowed to warm up to RT. It was stirred for an additional 6h at RT, hydrolyzed with water and extracted with EtOAc. The combined organic extracts were evaporated, dissolved in ether (50 ml) and treated with conc. HCl (10 ml) for 30 min at reflux. The mixture was neutralized with NaOH (10M) and extracted with EtOAc. The combined organic extracts were dried over MgSO4 and evaporated. Glass col. Chrom. (10-50% EtOAc in Hex) gave 3-(benzyloxy)cyclobutanone as a yellow oil. was added The mixture was cooled down to −78° C. The reaction was stirred over night to warm up to RT extracted with EtOAc The combined organic extracts were evaporated dissolved in ether (50 ml) treated with conc. HCl (10 ml) for 30 min at reflux extracted with EtOAc The combined organic extracts were dried over MgSO4 evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11 Parts of 2-benzyloxy-1,3-dibromo-propane, 30 parts of iso-propylamine and 30 parts of water were added to a stainless autoclave, and the mixture was heated at 80° C. for 2 hours with agitation. The reaction mixture was cooled and treated in the same manner as in Example 29, followed by distillation under reduced pressure. As a result, 18 parts of 3-benzyloxy-1-(iso-propyl)azetidine boiling at 104°-107° C. under 2 mm Hg were obtained. The reaction mixture was cooled treated in the same manner as in Example 29 followed by distillation under reduced pressure

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

Procedure: 2.5 M of n-butyllithium in hexane (19 mL) was added to a solution of (methylsulfinyl)(methylthio)methane (5.0 g, 0.040 mol) in THF (10 mL) dropwise at −10° C. and the mixture was stirred for 3 h. To the resultant solution was added dropwise [2-bromo-1-(bromomethyl)ethoxy]methylbenzene (4.9 g, 0.016 mol) at −70° C. over 30 min. The mixture was stirred at this temperature for 3 h and then at rt over night. The reaction was diluted with dichloromethane and washed with water. The aqueous phases were extracted with dichloromethane. The organic layers were combined, washed with brine, dried over MgSO4, concentrated and purified with Combiflash (silica gel, 0-55% EtOAc/Hex) to give the desired product (2.4 g, 56%) as brown oil. LCMS (M+Na) 293.3. 1H NMR (400 MHz, CDCl3): δ 7.30 (5H, m), 4.45 (2H, s), 4.33 (1H, m), 2.75 (2H, m), 2.65 (2H, m), 2.41 (3H, s), 2.12 (3H, s) ppm. The mixture was stirred at this temperature for 3 h at rt over night washed with water The aqueous phases were extracted with dichloromethane washed with brine dried over MgSO4 concentrated purified with Combiflash (silica gel, 0-55% EtOAc/Hex)