(1-chloro-2-methylpropan-2-yl)benzene

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

Procedure: By procedures described in Example 1 (Method B), 1-chloro-2-methyl-2-phenyl-propane and acetonitrile were converted to 1-methyl-4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline. A reaction vessel was charged with 4.0 g of this isoquinoline compound and 50 ml methylene chloride. With this mixture stirred, 2 ml dichloroacetyl chloride was added dropwise to the mixture. The mixture was stirred for 20 minutes and then made alkaline with aqueous sodium hydroxide. The organic extract was dried with magnesium sulfate and stripped of solvent. The residue was recrystallized from ethanol to provide 4.2 g of a white cubic-crystal product having the elemental analysis reported in Table I. The mixture was stirred for 20 minutes The organic extract was dried with magnesium sulfate The residue was recrystallized from ethanol

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

Procedure: By procedures described in Example 1 (Method B), 1-chloro-2-methyl-2-phenyl-propane and acetonitrile were converted to 1-methyl-4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline. A reaction vessel was charged with 4.0 g of this isoquinoline compound and 50 ml methylene chloride. With this mixture stirred, 2 ml dichloroacetyl chloride was added dropwise to the mixture. The mixture was stirred for 20 minutes and then made alkaline with aqueous sodium hydroxide. The organic extract was dried with magnesium sulfate and stripped of solvent. The residue was recrystallized from ethanol to provide 4.2 g of a white cubic-crystal product having the elemental analysis reported in Table I. The mixture was stirred for 20 minutes The organic extract was dried with magnesium sulfate The residue was recrystallized from ethanol

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of magnesium (4.48 g, 187 mmol), 1-chloro-2-methyl-2-phenylpropane (30.0 g, 179 mmol), a small amount of iodine and tetrahydrofuran (100 ml) was stirred at 70° C. for 2.5 hours. Then, the reaction mixture was cooled to 0° C., followed by adding dropwise thereto a solution of N-formylmorpholine (24.6 g, 214 mmol) in tetrahydrofuran (45 ml), and the resulting mixture was stirred at room temperature for 2 hours. Subsequently, the reaction mixture was re-cooled to 0° C. and 3N hydrochloric acid (180 ml) was added thereto, followed by stirring at room temperature. The reaction mixture was extracted with ethyl acetate, and the extract solution was washed successively with an aqueous sodium thiosulfate solution, an aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography to obtain 18.0 g of 3,3-dimethyl-3-phenylpropionaldehyde. by adding dropwise Subsequently, the reaction mixture was re-cooled to 0° C. The reaction mixture was extracted with ethyl acetate the extract solution was washed successively with an aqueous sodium thiosulfate solution an aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified by a silica gel column chromatography

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

Procedure: In a flask under argon were placed magnesium turnings (0.8 g, 0.036 mol), dry THF (10 mL) and a iodine crystal. Then, 1-chloro-2-methyl-2-phenylpropane (5 mL, 0.031 mol) in THF (15 mL) was added slowly and the reaction mixture was refluxed for 30 min. It was then allowed to cool to room temperature and finally it was cooled to -70° C. and sulfuryl chloride (2.5 mL, 0.031 mol) in THF (10 mL) was added dropwise. The reaction was allowed to warm up to room temperature and was stirred at this temperature overnight. The resulting solution was poured into diluted phosphate buffer and extracted with EtOAc (3×). Evaporation of the solvent afforded the title compound (4.6 g, 65%). In a flask under argon were placed the reaction mixture was refluxed for 30 min finally it was cooled to -70° C. to warm up to room temperature extracted with EtOAc (3×) Evaporation of the solvent

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-chloro-2-methyl-2-phenylpropane (150 g, 0.889 mol) and NaCN (54.46 g) in DMSO (250 mL) was heated at 100° C. for 3 weeks. The solution was concentrated to half the initial volume, H2O (400 mL) was added and it was extracted with Et2O (3×). The combined organic extracts were dried and concentrated to a crude product (115.1 g), which was directly used in the next step as obtained. The solution was concentrated to half the initial volume, H2O (400 mL) was added it was extracted with Et2O (3×) The combined organic extracts were dried concentrated to a crude product (115.1 g), which as obtained

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-chloro-2-methyl-2-phenylpropane (150 g, 0.889 mol) and NaCN (54.46 g) in DMSO (250 mL) was heated at 100° C. for 3 weeks. The solution was concentrated to half the initial volume, H2O (400 mL) was added and it was extracted with Et2O (3×). The combined organic extracts were dried and concentrated to a crude product (115.1 g), which was directly used in the next step as obtained. The solution was concentrated to half the initial volume, H2O (400 mL) was added it was extracted with Et2O (3×) The combined organic extracts were dried concentrated to a crude product (115.1 g), which as obtained

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

Procedure: Magnesium (4,86 g, 0.2 mol, 50-150 mesh), neophylchloride (0.2 g) and tetrahydrofurane(10 ml) were placed in a flask under an atmosphere of argon. A Grignard reaction was then started with 1,2-dibromoethane (0.2 ml). Neophylchloride (35,47 g, 0.2 mol) dissolved in MTBE (50 ml) was then added at reflux over a period of 50 minutes. After stirring for 2½ h at the same temperature, the reaction mixture was diluted with MTBE and dried CO2 was introduced above the surface at a temperature of 35° C. (ice cooling). The mixture was then acidified with HCl and extracted with MTBE. GC revealed the presence of 2,5-dimethyl-2,5-diphenyl-hexane and phenylisobutyric in a ratio of 54:46. A Grignard reaction was then added at reflux over a period of 50 minutes was introduced above the surface at a temperature of 35° C. (ice cooling) extracted with MTBE