2-(hydroxymethyl)-4-methylpentanoic acid

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diisopropylamine (20.6 g) is dissolved in 80 ml of dry tetrahydrofuran. This solution is cooled to -30° C. n-Butyllithium (77 ml of 2.6 M in hexane) is added dropwise in a nitrogen atmosphere at a rate that maintains the reaction at -30° to -20° C. This solution is stirred at -20° C. for 30 minutes. Isocaproic acid (11.6 g) in 10 ml of tetrahydrofuran is added dropwise at -20° to -10° C., then stirred at -10° C. for 30 minutes. In a separate flask, paraformaldehyde (28 g) is heated to about 200° C. and the vapors are carried in a stream of nitrogen over the surface of the tetrahydrofuran solution of the dilithium salt of isocaproic acid. During this procedure the temperature is kept between -10° and +10° C. After all of the paraformaldehyde has vaporized the reaction mixture is cooled to 0° C. and 10% hydrochloric acid is added dropwise until the reaction mixture becomes acidic. Product is extracted with 2 portions of ether (400 ml each). The ether is dried with magnesium sulfate, filtered and concentrated in vacuo to yield 13.2 g of crude material. Product is vacuum distilled to yield 9.0 g, boiling point 135°-142° C./9 mm of Hg. is added dropwise in a nitrogen atmosphere at a rate the reaction at -30° to -20° C stirred at -10° C. for 30 minutes is kept between -10° and +10° C is cooled to 0° C. Product is extracted with 2 portions of ether (400 ml each) The ether is dried with magnesium sulfate filtered concentrated in vacuo

反応条件: temp:270.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(Hydroxymethyl)-4-methylpentanoic acid (8.7 g) is heated with 10 drops of 85% phosphonic acid in a Wood's metal bath at 220° C. for 20 minutes. A distillation head is attached and the pressure is slowly decreased to 60 mm while the temperature is increased to 270° C. Product starts to distill and the pressure is further decreased to 10 mm. The vapor temperature varies between 180° and 190° C. The yield of the title compound as distillate is 7.0 g. to distill The vapor temperature varies between 180° and 190° C

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diisopropylamine (20.6 g) is dissolved in 80 ml of dry tetrahydrofuran. This solution is cooled to -30° C. n-Butyllithium (77 ml of 2.6 M in hexane) is added dropwise in a nitrogen atmosphere at a rate that maintains the reaction at -30° to -20° C. This solution is stirred at -20° C. for 30 minutes. Isocaproic acid (11.6 g) in 10 ml of tetrahydrofuran is added dropwise at -20° to -10° C., then stirred at -10° C. for 30 minutes. In a separate flask, paraformaldehyde (28 g) is heated to about 200° C. and the vapors are carried in a stream of nitrogen over the surface of the tetrahydrofuran solution of the dilithium salt of isocaproic acid. During this procedure the temperature is kept between -10° and +10° C. After all of the paraformaldehyde has vaporized the reaction mixture is cooled to 0° C. and 10% hydrochloric acid is added dropwise until the reaction mixture becomes acidic. Product is extracted with 2 portions of ether (400 ml each). The ether is dried with magnesium sulfate, filtered and concentrated in vacuo to yield 13.2 g of crude material. Product is vacuum distilled to yield 9.0 g, boiling point 135°-142° C./9 mm of Hg. is added dropwise in a nitrogen atmosphere at a rate the reaction at -30° to -20° C stirred at -10° C. for 30 minutes is kept between -10° and +10° C is cooled to 0° C. Product is extracted with 2 portions of ether (400 ml each) The ether is dried with magnesium sulfate filtered concentrated in vacuo

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diisopropylamine (20.6 g) is dissolved in 80 ml of dry tetrahydrofuran. This solution is cooled to -30° C. n-Butyllithium (77 ml of 2.6 M in hexane) is added dropwise in a nitrogen atmosphere at a rate that maintains the reaction at -30° to -20° C. This solution is stirred at -20° C. for 30 minutes. Isocaproic acid (11.6 g) in 10 ml of tetrahydrofuran is added dropwise at -20° to -10° C., then stirred at -10° C. for 30 minutes. In a separate flask, paraformaldehyde (28 g) is heated to about 200° C. and the vapors are carried in a stream of nitrogen over the surface of the tetrahydrofuran solution of the dilithium salt of isocaproic acid. During this procedure the temperature is kept between -10° and +10° C. After all of the paraformaldehyde has vaporized the reaction mixture is cooled to 0° C. and 10% hydrochloric acid is added dropwise until the reaction mixture becomes acidic. Product is extracted with 2 portions of ether (400 ml each). The ether is dried with magnesium sulfate, filtered and concentrated in vacuo to yield 13.2 g of crude material. Product is vacuum distilled to yield 9.0 g, boiling point 135°-142° C./9 mm of Hg. is added dropwise in a nitrogen atmosphere at a rate the reaction at -30° to -20° C stirred at -10° C. for 30 minutes is kept between -10° and +10° C is cooled to 0° C. Product is extracted with 2 portions of ether (400 ml each) The ether is dried with magnesium sulfate filtered concentrated in vacuo

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diisopropylamine (20.6 g) is dissolved in 80 ml of dry tetrahydrofuran. This solution is cooled to -30° C. n-Butyllithium (77 ml of 2.6 M in hexane) is added dropwise in a nitrogen atmosphere at a rate that maintains the reaction at -30° to -20° C. This solution is stirred at -20° C. for 30 minutes. Isocaproic acid (11.6 g) in 10 ml of tetrahydrofuran is added dropwise at -20° to -10° C., then stirred at -10° C. for 30 minutes. In a separate flask, paraformaldehyde (28 g) is heated to about 200° C. and the vapors are carried in a stream of nitrogen over the surface of the tetrahydrofuran solution of the dilithium salt of isocaproic acid. During this procedure the temperature is kept between -10° and +10° C. After all of the paraformaldehyde has vaporized the reaction mixture is cooled to 0° C. and 10% hydrochloric acid is added dropwise until the reaction mixture becomes acidic. Product is extracted with 2 portions of ether (400 ml each). The ether is dried with magnesium sulfate, filtered and concentrated in vacuo to yield 13.2 g of crude material. Product is vacuum distilled to yield 9.0 g, boiling point 135°-142° C./9 mm of Hg. is added dropwise in a nitrogen atmosphere at a rate the reaction at -30° to -20° C stirred at -10° C. for 30 minutes is kept between -10° and +10° C is cooled to 0° C. Product is extracted with 2 portions of ether (400 ml each) The ether is dried with magnesium sulfate filtered concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The compounds of formula I can be prepared using as a starting material 2-(hydroxymethyl)-4-methylpentanoic acid. Heating the starting material with phosphonic acid yields 4-methyl-2-methylenepentanoic acid which can in turn be reacted with a thio acid having the formula The compounds of formula I can be prepared

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diisopropylamine (20.6 g) is dissolved in 80 ml of dry tetrahydrofuran. This solution is cooled to -30° C. n-Butyllithium (77 ml of 2.6 M in hexane) is added dropwise in a nitrogen atmosphere at a rate that maintains the reaction at -30° to -20° C. This solution is stirred at -20° C. for 30 minutes. Isocaproic acid (11.6 g) in 10 ml of tetrahydrofuran is added dropwise at -20° to -10° C., then stirred at -10° C. for 30 minutes. In a separate flask, paraformaldehyde (28 g) is heated to about 200° C. and the vapors are carried in a stream of nitrogen over the surface of the tetrahydrofuran solution of the dilithium salt of isocaproic acid. During this procedure the temperature is kept between -10° and +10° C. After all of the paraformaldehyde has vaporized the reaction mixture is cooled to 0° C. and 10% hydrochloric acid is added dropwise until the reaction mixture becomes acidic. Product is extracted with 2 portions of ether (400 ml each). The ether is dried with magnesium sulfate, filtered and concentrated in vacuo to yield 13.2 g of crude material. Product is vacuum distilled to yield 9.0 g, boiling point 135°-142° C./9 mm of Hg. is added dropwise in a nitrogen atmosphere at a rate the reaction at -30° to -20° C stirred at -10° C. for 30 minutes is kept between -10° and +10° C is cooled to 0° C. Product is extracted with 2 portions of ether (400 ml each) The ether is dried with magnesium sulfate filtered concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The compounds of formula I can be prepared using as a starting material 2-(hydroxymethyl)-4-methylpentanoic acid. Heating the starting material with phosphonic acid yields 4-methyl-2-methylenepentanoic acid which can in turn be reacted with a thio acid having the formula The compounds of formula I can be prepared