1-chloro-3,3-dimethylbutane

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

Procedure: As a known compound, t-butylethyl, (i.e., 3,3-dimethylbutyl) diphenyl phosphine was also synthesized via the known displacement approach: the reaction of lithium diphenyl phosphide with 3,3-dimethylbutyl chloride provided the compound in good yield. provided the compound in good yield

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of thiophene (300 mg, 3.57 mmol) in anhydrous 10% hexamethylphosphoramide in tetrahydrofuran (33 mL) under argon at −78° C. was added n-butyllithium (1.57 mL, 2.5 M in hexanes) dropwise. After stirring at −78° C. for 1 hour, 1-chloro-3,3-dimethylbutane (430 mg, 3.57 mmol) was added dropwise and the resulting solution allowed to warm to room temperature over 3 hours. The reaction mixture was re-cooled to −78° C., a second portion of n-butyllithium (1.78 mL, 4.46 mmol) was added dropwise over 5 minutes and the mixture was stirred for 1 hour at −78° C. before anhydrous dimethylformamide (1.38 mL, 17.8 mmol) was added dropwise and the resulting mixture allowed to warm to room temperature. The reaction mixture was poured into 1 N hydrochloric acid (150 mL) and organics were extracted with ether (3×100 mL), dried with magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel with gradient elution (5%→20% ethyl acetate in hexanes) to give 5-(3,3-dimethylbutyl)thiophene-2-carbaldehyde (130 mg, 19%). Used without further characterization. to warm to room temperature over 3 hours The reaction mixture was re-cooled to −78° C. was added dropwise to warm to room temperature organics were extracted with ether (3×100 mL) dried with magnesium sulfate filtered concentrated The residue was purified by flash chromatography on silica gel with gradient elution (5%→20% ethyl acetate in hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of thiophene (300 mg, 3.57 mmol) in anhydrous 10% hexamethylphosphoramide in tetrahydrofuran (33 mL) under argon at −78° C. was added n-butyllithium (1.57 mL, 2.5 M in hexanes) dropwise. After stirring at −78° C. for 1 hour, 1-chloro-3,3-dimethylbutane (430 mg, 3.57 mmol) was added dropwise and the resulting solution allowed to warm to room temperature over 3 hours. The reaction mixture was re-cooled to −78° C., a second portion of n-butyllithium (1.78 mL, 4.46 mmol) was added dropwise over 5 minutes and the mixture was stirred for 1 hour at −78° C. before anhydrous dimethylformamide (1.38 mL, 17.8 mmol) was added dropwise and the resulting mixture allowed to warm to room temperature. The reaction mixture was poured into 1 N hydrochloric acid (150 mL) and organics were extracted with ether (3×100 mL), dried with magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel with gradient elution (5%→20% ethyl acetate in hexanes) to give 5-(3,3-dimethylbutyl)thiophene-2-carbaldehyde (130 mg, 19%). Used without further characterization. to warm to room temperature over 3 hours The reaction mixture was re-cooled to −78° C. was added dropwise to warm to room temperature organics were extracted with ether (3×100 mL) dried with magnesium sulfate filtered concentrated The residue was purified by flash chromatography on silica gel with gradient elution (5%→20% ethyl acetate in hexanes)

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

Procedure: A suspension of 4-hydroxybenzaldehyde (200 mg, 1.64 mmol), 1-chloro-3,3-dimethylbutane (395 mg, 1.97 mmol), sodium iodide (24 mg, 0.16 mmol), and cesium carbonate (800 mg, 2.46 mmol) in anhydrous dimethylformamide (5 mL) was stirred at 80° C. overnight. After cooling to room temperature, solids were filtered and washed with ether. The filtrate was washed with 2 N sodium hydroxide (2×20 mL), water (20 mL), and brine (20 mL), dried over magnesium sulfate, filtered, and concentrated to give 4-(3,3-dimethylbutoxyl)benzaldehyde (262 mg, 78% crude) as a pale yellow oil that was used without further purification or characterization. After cooling to room temperature solids were filtered washed with ether The filtrate was washed with 2 N sodium hydroxide (2×20 mL), water (20 mL), and brine (20 mL) dried over magnesium sulfate filtered concentrated

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

Procedure: Sodium 3-piperidinopropanolate (5 mmol), 5 mmol of 3,3-dimethylbutyl chloride, a catalytic amount of tetrabutylammonium iodide, and 0.5 mmol of 15-crown-5 in 10 ml of dry dimethyl sulfoxide were refluxed for 12 hours. Water was added, and it was extracted with diethyl ether. The organic layer was purified by column chromatography on silica gel (eluent: methylene chloride/methanol (90/10), ammonia atmosphere). The solvent was removed under reduced pressure and the residue crystallized with oxalic acid from diethyl ether/ethanol. it was extracted with diethyl ether The organic layer was purified by column chromatography on silica gel (eluent: methylene chloride/methanol (90/10), ammonia atmosphere) The solvent was removed under reduced pressure the residue crystallized with oxalic acid from diethyl ether/ethanol

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction vessel was charged with 12.16 g. (0.5 g.atom) of magnesium chips and 15 c.c. of a solution containing 60.3 g. (0.5 mole) 1-chloro-3,3-dimethylbutane dissolved in 200 c.c. of tetrahydrofuran. A nitrogen atmosphere was established within the vessel. The reaction was initiated by the addition of a few drops of ethylene dibromide, whereupon the remaining portion of the aforementioned tetrahydrofuran solution was added over a period of 1.5 hours. External heating was applied to maintain the reaction mixture at the boiling point. Heating was continued for 1 hour following completion of the addition, at which time the liquid phase was separated from the unreacted magnesium (0.32 g.) by decantation. A portion of this liquid phase containing 0.44 mole of 3,3-dimethylbutylmagnesium chloride was charged into a reaction vessel containing a nitrogen atmosphere. A solution of 31.2 g. (0.13 mole) of methyltin trichloride dissolved in 100 c.c. benzene was gradually added over 0.33 hours to the stirred contents of the reaction vessel. External cooling was applied as required to maintain the reaction mixture at 40° C. Following completion of the addition the resultant mixture was stirred for about 16 hours at ambient temperature, after which the contents of the reaction vessel were heated at the boiling point for 1 hour, then hydrolyzed using a solution of citric acid (50 g.) in 250 c.c. water. The organic phase was then separated, dried using a portion of anhydrous magnesium sulfate and the organic solvents removed under reduced pressure while the mixture was maintained at a temperature of about 40° C. The resultant colorless oil, obtained in 97% yield, was purified by combining a 35 g. portion of the oil with methanol, cooling the mixture to -20° C. and triturating the semi-solid mass. The white solid was isolated and recrystallized using a 60/40 volume ratio mixture of methanol/ethanol to yield methyl tris(3,3-dimethylbutyl)tin in 56% yield, based on starting materials. A reaction vessel was charged with 12.16 g of a solution containing 60.3 g was added over a period of 1.5 hours External heating to maintain the reaction mixture at the boiling point Heating completion of the addition at which time the liquid phase was separated from the unreacted magnesium (0.32 g.) by decantation was charged into a reaction vessel containing a nitrogen atmosphere External cooling after which the contents of the reaction vessel were heated at the boiling point for 1 hour The organic phase was then separated dried the organic solvents removed under reduced pressure while the mixture was maintained at a temperature of about 40° C The resultant colorless oil, obtained in 97% yield was purified portion of the oil with methanol, cooling the mixture to -20° C. triturating the semi-solid mass The white solid was isolated recrystallized a 60/40 volume ratio mixture of methanol/ethanol

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction vessel was charged with 12.16 g. (0.5 g.atom) of magnesium chips and 15 c.c. of a solution containing 60.3 g. (0.5 mole) 1-chloro-3,3-dimethylbutane dissolved in 200 c.c. of tetrahydrofuran. A nitrogen atmosphere was established within the vessel. The reaction was initiated by the addition of a few drops of ethylene dibromide, whereupon the remaining portion of the aforementioned tetrahydrofuran solution was added over a period of 1.5 hours. External heating was applied to maintain the reaction mixture at the boiling point. Heating was continued for 1 hour following completion of the addition, at which time the liquid phase was separated from the unreacted magnesium (0.32 g.) by decantation. A portion of this liquid phase containing 0.44 mole of 3,3-dimethylbutylmagnesium chloride was charged into a reaction vessel containing a nitrogen atmosphere. A solution of 31.2 g. (0.13 mole) of methyltin trichloride dissolved in 100 c.c. benzene was gradually added over 0.33 hours to the stirred contents of the reaction vessel. External cooling was applied as required to maintain the reaction mixture at 40° C. Following completion of the addition the resultant mixture was stirred for about 16 hours at ambient temperature, after which the contents of the reaction vessel were heated at the boiling point for 1 hour, then hydrolyzed using a solution of citric acid (50 g.) in 250 c.c. water. The organic phase was then separated, dried using a portion of anhydrous magnesium sulfate and the organic solvents removed under reduced pressure while the mixture was maintained at a temperature of about 40° C. The resultant colorless oil, obtained in 97% yield, was purified by combining a 35 g. portion of the oil with methanol, cooling the mixture to -20° C. and triturating the semi-solid mass. The white solid was isolated and recrystallized using a 60/40 volume ratio mixture of methanol/ethanol to yield methyl tris(3,3-dimethylbutyl)tin in 56% yield, based on starting materials. A reaction vessel was charged with 12.16 g of a solution containing 60.3 g was added over a period of 1.5 hours External heating to maintain the reaction mixture at the boiling point Heating completion of the addition at which time the liquid phase was separated from the unreacted magnesium (0.32 g.) by decantation was charged into a reaction vessel containing a nitrogen atmosphere External cooling after which the contents of the reaction vessel were heated at the boiling point for 1 hour The organic phase was then separated dried the organic solvents removed under reduced pressure while the mixture was maintained at a temperature of about 40° C The resultant colorless oil, obtained in 97% yield was purified portion of the oil with methanol, cooling the mixture to -20° C. triturating the semi-solid mass The white solid was isolated recrystallized a 60/40 volume ratio mixture of methanol/ethanol

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

Procedure: To a suspension of magnesium turnings (2.90 g, 0.12 mol) in tetrahydrofuran (150 mL) was added 1-chloro-3,3-dimethylbutane (14.2 g, 0.12 mol). The mixture was cooled to 0° C. and dibromoethane (2.5 mL, 29 mmol) was added portion wise over 15 min. The mixture was allowed to warm to room temperature and stirred for 1 h. After which, an additional equivalent of dibromoethane (2.5 mL, 29 mmol) was added portion wise over 15 min and stirred at room temperature for 72 h. The mixture was diluted with tetrahydrofuran (50 mL) cooled to −78° C., and treated with titanium(IV) isopropoxide (33.9 mL, 0.11 mol). The reaction mixture was stirred at −78° C. for 1 h and a solution of 2-hydroxy-1,4-naphthoquinone (5.0 g, 29 mmol) in tetrahydrofuran (80 mL) pre-cooled to 0° C. was added via a cannula. After addition, the solution was warmed to room temperature and stirred for 18 h. The solution was diluted with ethyl acetate (250 mL) and washed with aqueous 1 N HCl (2×100 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. Column chromatography on florisil (dichloromethane→1%→3→%5% methanol/dichloromethane) followed by second column chromatography on silica (30%→50% ethyl acetate/hexane) afforded the title compound as an orange amorphous solid (2.06 g, 28%). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.33-0.52 (m, 1H), 0.68 (s, 9H), 0.77-0.92 (m, 1H), 1.67-1.84 (m, 1H), 1.88-2.11 (m, 1H), 5.56 (s, 1H), 7.36-7.45 (m, 1H), 7.57 (t, J=6.99 Hz, 1H), 7.62-7.68 (m, 1H), 7.82 (d, J=6.62 Hz, 1H); MS m/z 261.1 (M+H)+. to warm to room temperature stirred at room temperature for 72 h cooled to −78° C. The reaction mixture was stirred at −78° C. for 1 h was added via a cannula After addition the solution was warmed to room temperature stirred for 18 h washed with aqueous 1 N HCl (2×100 mL) The organic layer was dried (Na2SO4) concentrated in vacuo

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

Procedure: 5 g (22.9 millimoles) of N-(4-tert-butylphenyl)-piperazine, 8.3 g (68.7 millimoles) of neohexyl chloride, 3.2 g (22.9 millimoles) of potassium carbonate and 3.8 g (22.9 millimoles) of potassium iodide are stirred for 16 hours at 140° C. The mixture is taken up in dichloromethane and dilute sodium hydroxide solution. The organic phase is washed, dried over sodium sulfate and evaporated down under reduced pressure, and the residue is chromatographed over silica gel using 1:1 methyl tert-butyl ether/hexane to give 1.5 g (22% of theory) of a colourless oil (for IR data, see Table 1a). The organic phase is washed dried over sodium sulfate evaporated down under reduced pressure the residue is chromatographed over silica gel using 1:1 methyl tert-butyl ether/hexane to give 1.5 g (22% of theory) of a colourless oil (for IR data, see Table 1a)

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

Procedure: As a known compound, t-butylethyl, (i.e., 3,3-dimethylbutyl)diphenyl phosphine was also synthesized via the known displacement approach: the reaction of lithium diphenyl phosphide with 3,3-dimethylbutyl chloride provided the compound in good yield. provided the compound in good yield

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

Procedure: As a known compound, t-butylethyl, i.e., 3,3-dimethylbutyl, diphenyl phosphine, was also synthesized via the known displacement approach: the reaction of lithium diphenyl phosphide with 3,3-dimethylbutyl chloride provided the compound in good yield. provided the compound in good yield

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

Procedure: As a known compound, t-butylethyl, (i.e., 3,3-dimethylbutyl) diphenyl phosphine was also synthesized via the known displacement approach: the reaction of lithium diphenyl phosphide with 3,3-dimethylbutyl chloride provided the compound in good yield. provided the compound in good yield