1-chloro-2-methylpropane

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

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

Procedure: In an isobutylmagnesium chloride solution that was prepared by reacting isobutyl chloride (3.74 g, 40 mmol) and magnesium (0.97 g, 40 mmol) in dry ether (40 ml) at 0° C., dichlorobis(π-cyclopentadienyl)titanium (0.22 g, 0.9 mmol) and 1,1,1-trifluoro-4-phenyl-3-butyne-2-ol (2 g, 10 mmol) were slowly added at 0° C. After 4 hour agitation of the mixture at room temperature, solvent was removed under heating for 30 min. Next, dry tetrahydrofuran (20 ml) was put into the reaction vessel and further methyl iodide (12.7 g, 90 mmol) was slowly added. After 12 hour agitation, the reaction mixture was treated by a method similar to the one in the above Examples to obtain (Z)-1,1,1-trifluoro-4-phenyl-3-pentene-2-ol (b.p.: 84°-86° C./2 mmHg) at a yield of 63%. The above product gave the following analytical data: at 0° C. solvent was removed under heating for 30 min was slowly added After 12 hour agitation

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

Procedure: In an isobutylmagnesium chloride solution that was prepared by reacting isobutyl chloride (2.34 g, 25 mmol) and magnesium (0.66 g, 27 mmol) in dry ether (30 ml) at 0° C., dichlorobis(π-cyclopentadienyl)titanium (0.14 g, 0.56 mmol) and 1,1,1,-trifluoro-4-phenyl-3-butyne-2-ol (2g, 10 mmol) were slowly added at 0° C. After 1 hour agitation at the same temperature, the reaction mixture was treated by a method similar to the one in the above Examples to obtain (Z)-1,1,1-trifluoro-4-phenyl-3-butene-2-ol (b.p.: 78°-80° C./3 mmHg) at a yield of 53%. The above product gave the following analytical data: at 0° C.

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

Procedure: The titled compound (10 mg) as a white solid was prepared from the compound [4-6] obtained in the process (6) of Example 4 (100 mg) and isobutyl chloride according to the method of the process (7) of Example 4.

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

Procedure: In an isobutylmagnesium chloride solution that was prepared by reacting isobutyl chloride (3.74 g, 40 mmol) and magnesium (0.97 g, 40 mmol) in dry ether (40 ml) at 0° C., dichlorobis(π-cyclopentadienyl)titanium (0.22 g, 0.9 mmol) and 1,1,1-trifluoro-4-phenyl-3-butyne-2-ol (2 g, 10 mmol) were slowly added at 0° C. After 4 hour agitation of the mixture at room temperature, solvent was removed under heating for 30 min. Next, dry tetrahydrofuran (20 ml) was put into the reaction vessel and further methyl iodide (12.7 g, 90 mmol) was slowly added. After 12 hour agitation, the reaction mixture was treated by a method similar to the one in the above Examples to obtain (Z)-1,1,1-trifluoro-4-phenyl-3-pentene-2-ol (b.p.: 84°-86° C./2 mmHg) at a yield of 63%. The above product gave the following analytical data: at 0° C. solvent was removed under heating for 30 min was slowly added After 12 hour agitation

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

Procedure: In an isobutylmagnesium chloride solution that was prepared by reacting isobutyl chloride (2.34 g, 25 mmol) and magnesium (0.66 g, 27 mmol) in dry ether (30 ml) at 0° C., dichlorobis(π-cyclopentadienyl)titanium (0.14 g, 0.56 mmol) and 1,1,1,-trifluoro-4-phenyl-3-butyne-2-ol (2g, 10 mmol) were slowly added at 0° C. After 1 hour agitation at the same temperature, the reaction mixture was treated by a method similar to the one in the above Examples to obtain (Z)-1,1,1-trifluoro-4-phenyl-3-butene-2-ol (b.p.: 78°-80° C./3 mmHg) at a yield of 53%. The above product gave the following analytical data: at 0° C.

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

Procedure: In an isobutylmagnesium chloride solution that was prepared by reacting isobutyl chloride (2.34 g, 25 mmol) and magnesium (0.66 g, 27 mmol) in dry ether (30 ml) at 0° C., dichlorobis(π-cyclopentadienyl)titanium (0.14 g, 0.56 mmol) and 1,1,1,-trifluoro-4-phenyl-3-butyne-2-ol (2g, 10 mmol) were slowly added at 0° C. After 1 hour agitation at the same temperature, the reaction mixture was treated by a method similar to the one in the above Examples to obtain (Z)-1,1,1-trifluoro-4-phenyl-3-butene-2-ol (b.p.: 78°-80° C./3 mmHg) at a yield of 53%. The above product gave the following analytical data: at 0° C.

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

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

Procedure: 34.5 g of isobutyl chloride were added over 15 minutes to a mixture of 46.7 g of o-trifluoromethylaniline, 32.6 g of triethylamine and 470 ml of acetone and the mixture was held at 15° C for 30 minutes and then returned to room temperature. The mixture stood for 12 hours and was filtered and the filtrate was evaporated to dryness. The residue was taken up in 700 ml of ethyl acetate and the solution was washed with 10% potassium carbonate solution and then with water until the wash water pH was 6, then with N hydrochloric acid and finally with water until the wash water pH was 6. The solution was dried over magnesium sulfate, was treated with activated carbon and was evaporated to obtain 68 g of raw product which was washed with hexane to obtain 60 g of N-(2-trifluoromethylphenyl)-2-methyl-propanamide melting at 114° C which was used as is for the next step. returned to room temperature The mixture stood for 12 hours was filtered the filtrate was evaporated to dryness the solution was washed with 10% potassium carbonate solution The solution was dried over magnesium sulfate was treated with activated carbon was evaporated to obtain 68 g of raw product which was washed with hexane

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

Procedure: 34.5 g of isobutyl chloride were added over 15 minutes to a mixture of 46.7 g of o-trifluoromethylaniline, 32.6 g of triethylamine and 470 ml of acetone and the mixture was held at 15° C for 30 minutes and then returned to room temperature. The mixture stood for 12 hours and was filtered and the filtrate was evaporated to dryness. The residue was taken up in 700 ml of ethyl acetate and the solution was washed with 10% potassium carbonate solution and then with water until the wash water pH was 6, then with N hydrochloric acid and finally with water until the wash water pH was 6. The solution was dried over magnesium sulfate, was treated with activated carbon and was evaporated to obtain 68 g of raw product which was washed with hexane to obtain 60 g of N-(2-trifluoromethylphenyl)-2-methyl-propanamide melting at 114° C which was used as is for the next step. returned to room temperature The mixture stood for 12 hours was filtered the filtrate was evaporated to dryness the solution was washed with 10% potassium carbonate solution The solution was dried over magnesium sulfate was treated with activated carbon was evaporated to obtain 68 g of raw product which was washed with hexane

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

Procedure: 34.5 g of isobutyl chloride were added over 15 minutes to a mixture of 46.7 g of o-trifluoromethylaniline, 32.6 g of triethylamine and 470 ml of acetone and the mixture was held at 15° C for 30 minutes and then returned to room temperature. The mixture stood for 12 hours and was filtered and the filtrate was evaporated to dryness. The residue was taken up in 700 ml of ethyl acetate and the solution was washed with 10% potassium carbonate solution and then with water until the wash water pH was 6, then with N hydrochloric acid and finally with water until the wash water pH was 6. The solution was dried over magnesium sulfate, was treated with activated carbon and was evaporated to obtain 68 g of raw product which was washed with hexane to obtain 60 g of N-(2-trifluoromethylphenyl)-2-methyl-propanamide melting at 114° C which was used as is for the next step. returned to room temperature The mixture stood for 12 hours was filtered the filtrate was evaporated to dryness the solution was washed with 10% potassium carbonate solution The solution was dried over magnesium sulfate was treated with activated carbon was evaporated to obtain 68 g of raw product which was washed with hexane

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

Procedure: To a solution of (3S)-3-isopropyl-1,3-dihydro-isobenzofuran-1-ol (14.11 g, 0.129 mol) in THF (250 ml) was added at reflux temperature through a Teflon tube, which ended under the surface in the reaction mixture, a solution of isobutyl magnesium chloride (freshly prepared from 0.387 mol isobutyl chloride and 0.58 mol magnesium in 250 ml of THF) slowly within 20 minutes under efficient stirring. The mixture was then quenched with a solution of ammonium chloride (10%). The organic layer was separated, and the solvent was removed on the rotavapor. The residue was re-dissolved in ethyl acetate (200 ml), and this solution was washed with water (150 ml) and brine (150 ml). After drying and removal of the solvent the product was obtained as a yellow oil (31.5 g). 1H/13C-NMR (300 MHz, CDCl3, HSQC/HMBC) δ/δ 0.78 (d, J=6.9 Hz)/19.00, 1.04 (d, J=6.5 Hz)/20.22 (2 i-Pr CH3); 0.95 (d, J=6.5 Hz)/23.87, 0.96 (d, J=6.5 Hz)/22.32 (2 i-Bu CH3); 1.80 (m)/25.33 (i-Bu CHMe2); 2.02 (m)/35.13 ((i-Pr CHMe2); 1.47/1.72 (m)/48.03 (CH2); 3.09 (br s, 2 OH); 4.53 (d, J=8.1 Hz)/77.55 (CH(OH)i-Pr); 5.08 (dd, J=4.7 Hz, J=9.5 Hz)/68.87 (CH(OH)i-Bu); 7.40 (m)/126.44 (Ar i-Bu ortho-CH); 7.21 (m)/127.37 (Ar meta-CH); 7.28 (m)/127.55 (Ar i-Pr ortho-CH); 7.23 (m)/127.71 (Ar meta-CH); 140.56 (Ar i-Pr ipso-C); 142.66 (Ar i-Bu ipso-CH). at reflux temperature through a Teflon tube The mixture was then quenched with a solution of ammonium chloride (10%) The organic layer was separated the solvent was removed on the rotavapor The residue was re-dissolved in ethyl acetate (200 ml) this solution was washed with water (150 ml) and brine (150 ml) After drying removal of the solvent the product