4-chlorobutoxybenzene

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:

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

Conditions: temp:88.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Chlorobutoxy) benzene (320 mg, 1.39 mmol) in EtOH (17 Ml) was treated with DIEA (0.48 Ml, 2.78 mmol) and 1-(2-methylbenzothiazol-5-yloxy)-3-piperazin-1-ylpropan-2-ol as prepared in Example 3A (427 mg, 1.39 mmol), then stirred 14 hours at 88° C. Upon cooling, concentrated in vacuo and purified on the Isco™ (10 g Redisep™ columns, 100% EtOAc hold 2 min., 8 min. gradient to 20% MeOH/EtOAc, hold 10 min) to provide (2R)-3-(2-methylbenzothiazol-5-yloxy)-1-[4-(4-phenoxybutyl)piperazinyl]propan-2-ol. Upon cooling concentrated in vacuo purified on the Isco™ (10 g Redisep™ columns, 100% EtOAc hold 2 min., 8 min. gradient to 20% MeOH/EtOAc, hold 10 min)

Conditions: temp:88.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Chlorobutoxy) benzene (320 mg, 1.39 mmol) in EtOH (17 Ml) was treated with DIEA (0.48 Ml, 2.78 mmol) and 1-(2-methylbenzothiazol-5-yloxy)-3-piperazin-1-ylpropan-2-ol as prepared in Example 3A (427 mg, 1.39 mmol), then stirred 14 hours at 88° C. Upon cooling, concentrated in vacuo and purified on the Isco™ (10 g Redisep™ columns, 100% EtOAc hold 2 min., 8 min. gradient to 20% MeOH/EtOAc, hold 10 min) to provide (2R)-3-(2-methylbenzothiazol-5-yloxy)-1-[4-(4-phenoxybutyl)piperazinyl]propan-2-ol. Upon cooling concentrated in vacuo purified on the Isco™ (10 g Redisep™ columns, 100% EtOAc hold 2 min., 8 min. gradient to 20% MeOH/EtOAc, hold 10 min)

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

Procedure: To a stirred solution of 2-phenylbutyric acid (5.6 g, 34 mmol) in trifluoroacetic anhydrlde (20 ml) was added 4-chlorobutoxybenzene (7.5 g, 41 mmol). After 16 h, the mixture was poured into saturated sodium bicarbonate solution (250 ml), and extracted with ether (2×100 ml). The combined organic layers were dried (MgSO4), and concentrated in vacuo. The residues were purified by flash chromatography (silica; eluant:10-30% ethyl acetate in petrol) to give the title compound as an orange oil (10.6 g, 94% ). extracted with ether (2×100 ml) The combined organic layers were dried (MgSO4) concentrated in vacuo The residues were purified by flash chromatography (silica; eluant:10-30% ethyl acetate in petrol)

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

Procedure: A two phase mixture of phenol (5 g, 53 mmol), 1,4-dichlorobutane (30 ml), tetrabutylammonium hydrogen sulphate (0.3 g, 1 mmol), and sodium hydroxide solution (25 ml, 6M) was refluxed for 3 h. The organic layer was separated, dried (MgSO4), and concentrated in vacuo. The residues were purified by flash chromatography (silica (Merck 15111); eluant:petrol) to give the product as a colourless viscous oil (7.57 g 77%) bp 250° C. at 0.2 mm Hg. was refluxed for 3 h The organic layer was separated dried (MgSO4) concentrated in vacuo The residues were purified by flash chromatography (silica (Merck 15111); eluant:petrol)

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

Procedure: A two phase mixture of phenol (5 g, 53 mmol), 1,4-dichlorobutane (30 ml), tetrabutylammonium hydrogen sulphate (0.3 g, 1 mmol), and sodium hydroxide solution (25 ml, 6M) was refluxed for 3 h. The organic layer was separated, dried (MgSO4), and concentrated in vacuo. The residues were purified by flash chromatography (silica (Merck 15111); eluant:petrol) to give the product as a colourless viscous oil (7.57 g 77%) bp 250° C. at 0.2 mm Hg. was refluxed for 3 h The organic layer was separated dried (MgSO4) concentrated in vacuo The residues were purified by flash chromatography (silica (Merck 15111); eluant:petrol)

Conditions: temp:88.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Chlorobutoxy) benzene (320 mg, 1.39 mmol) in EtOH (17 Ml) was treated with DIEA (0.48 Ml, 2.78 mmol) and 1-(2-methylbenzothiazol-5-yloxy)-3-piperazin-1-ylpropan-2-ol as prepared in Example 3A (427 mg, 1.39 mmol), then stirred 14 hours at 88° C. Upon cooling, concentrated in vacuo and purified on the Isco™ (10 g Redisep™ columns, 100% EtOAc hold 2 min., 8 min. gradient to 20% MeOH/EtOAc, hold 10 min) to provide (2R)-3-(2-methylbenzothiazol-5-yloxy)-1-[4-(4-phenoxybutyl)piperazinyl]propan-2-ol. Upon cooling concentrated in vacuo purified on the Isco™ (10 g Redisep™ columns, 100% EtOAc hold 2 min., 8 min. gradient to 20% MeOH/EtOAc, hold 10 min)

Conditions: temp:88.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Chlorobutoxy) benzene (320 mg, 1.39 mmol) in EtOH (17 Ml) was treated with DIEA (0.48 Ml, 2.78 mmol) and 1-(2-methylbenzothiazol-5-yloxy)-3-piperazin-1-ylpropan-2-ol as prepared in Example 3A (427 mg, 1.39 mmol), then stirred 14 hours at 88° C. Upon cooling, concentrated in vacuo and purified on the Isco™ (10 g Redisep™ columns, 100% EtOAc hold 2 min., 8 min. gradient to 20% MeOH/EtOAc, hold 10 min) to provide (2R)-3-(2-methylbenzothiazol-5-yloxy)-1-[4-(4-phenoxybutyl)piperazinyl]propan-2-ol. Upon cooling concentrated in vacuo purified on the Isco™ (10 g Redisep™ columns, 100% EtOAc hold 2 min., 8 min. gradient to 20% MeOH/EtOAc, hold 10 min)