2-methylpropyl (2R)-2-hydroxypropanoate

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

Procedure: A mixture of isobutyl (R)-lactate (73 g, 0.5 mol, Merck) and 3,4-dihydro-2H-pyran (70 g, 0.83 mol, Merck) was treated with 5M hydrogen chloride in dimethylformamide (4 ml) and set aside at ambient temperature overnight in calcium chloride protected 250 ml round-bottom flask. Silver oxide (15 g) was added, the mixture stirred magnetically for 2 hours and then filtered. The product was isolated by distillation (13 Pa, b.p. 94-96° C.) to provide isobutyl 2-O-tetrahydropyranyl-(R)-lactate (102.5 g, 89%) as a colorless oil. filtered The product was isolated by distillation (13 Pa, b.p. 94-96° C.)

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

Procedure: A mixture of isobutyl (R)-lactate (73 g, 0.5 mol, Merck) and 3,4-dihydro-2H-pyran (70 g, 0.83 mol, Merck) was treated with 5M hydrogen chloride in dimethylformamide (4 ml) and set aside at ambient temperature overnight in calcium chloride protected 250 ml round-bottom flask. Silver oxide (15 g) was added, the mixture stirred magnetically for 2 hours and then filtered. The product was isolated by distillation (13 Pa, b.p. 94-96° C.) to provide isobutyl 2-O-tetrahydropyranyl-(R)-lactate (102.5 g, 89%) as a colorless oil. filtered The product was isolated by distillation (13 Pa, b.p. 94-96° C.)

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

Procedure: A mixture of isobutyl (R)-lactate (73 g, 0,5 mol, Merck) and 3,4-dihydro-2H-pyran (70 g, 0,83 mol, Merck) was treated with 5M hydrogen chloride in dimethylformamide (4 ml) and set aside at ambient temperature overnight in calcium chloride protected 250 ml round-bottom flask. Silver oxide (15 g) was added, the mixture stirred magnetically for 2 hours and then filtered. The product was isolated by distillation (13 Pa, b.p. 94-96° C.) to provide isobutyl 2-0-tetrahydropyranyl-(R)-lactate (102.5 g, 89%) as a colorless oil. filtered The product was isolated by distillation (13 Pa, b.p. 94-96° C.)

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

Procedure: A mixture of isobutyl (R)-lactate (73 g, 0.5 mol, Merck) and 3,4-dihydro-2H-pyran (70 g, 0.83 mol, Merck) was treated with 5M hydrogen chloride in dimethylformamide (4 ml) and set aside at ambient temperature overnight in calcium chloride protected 250 ml round-bottom flask. Silver oxide (15 g) was added, the mixture stirred magnetically for 2 hours and then filtered. The product was isolated by distillation (13 Pa, b.p. 94∝96° C.) to provide isobutyl 2-O-tetrahydropyranyl-(R)-lactate (102.5 g, 89%) as a colorless oil. filtered The product was isolated by distillation (13 Pa, b.p. 94∝96° C.)

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

Procedure: A mixture of isobutyl (R)-lactate (73 g, 0.5 mol, Merck) and 3,4-dihydro-2H-pyran (70 g, 0.83 mol, Merck) was treated with 5M hydrogen chloride in dimethylformamide (4 ml) and set aside at ambient temperature overnight in calcium chloride protected 250 ml round-bottom flask. Silver oxide (15 g) was added, the mixture stirred magnetically for 2 hours and then filtered. The product was isolated by distillation (13 Pa, b.p. 94∝96° C.) to provide isobutyl 2-O-tetrahydropyranyl-(R)-lactate (102.5 g, 89%) as a colorless oil. filtered The product was isolated by distillation (13 Pa, b.p. 94∝96° C.)

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

Procedure: 2.0 g of 60% sodium hydride was suspended in 50 ml of toluene. The suspension was cooled on an ice bath. Thereto was dropwise added 7.3 g of isobutyl (R)-(+)-lactate with stirring, followed by stirring for 1 hour. Thereto was dropwise added 5.0 g of chloromethoxymethane, followed by stirring for 3 hours. The reaction mixture was washed with 50 ml of a saturated aqueous sodium hydrogen carbonate solution and 30 ml of water in this order. The washed material was subjected to vacuum distillation to remove the solvent, whereby was obtained 9.0 g (yield: 86.6%) of an oily title compound. The suspension was cooled on an ice bath by stirring for 1 hour by stirring for 3 hours The reaction mixture was washed with 50 ml of a saturated aqueous sodium hydrogen carbonate solution and 30 ml of water in this order The washed material was subjected to vacuum distillation to remove the solvent

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

Procedure: A catalytic amount of pyridinium para-toluenesulfonate was added to 29.2 g (0.2 mole) of isobutyl (R)-(+)-lactate and 28.0 g (0.22 mole) of cyclohexyl vinyl ether. The resulting mixture was stirred at room temperature for 4 hours to give rise to a reaction. Thereto was added 100 ml of ethyl acetate, followed by washing with 100 ml of a saturated aqueous sodium hydrogen carbonate solution, 40 ml of water and 40 ml of a saturated aqueous sodium chloride solution in this order. The washed material was dried over anhydrous sodium sulfate and then subjected to vacuum distillation to remove the solvent, whereby was obtained 54.2 g (yield: 99.4%) of an oily title compound (diastereomixture). to give rise to a reaction by washing with 100 ml of a saturated aqueous sodium hydrogen carbonate solution, 40 ml of water and 40 ml of a saturated aqueous sodium chloride solution in this order The washed material was dried over anhydrous sodium sulfate subjected to vacuum distillation to remove the solvent

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

Procedure: A catalytic amount of pyridinium para-toluenesulfonate was added to 29.2 g (0.2 mole) of isobutyl (R)-(+)-lactate and 22.0 g (0.22 mole) of n-butyl vinyl ether. The resulting mixture was stirred at room temperature for 4 hours to give rise to a reaction. Thereto was added 100 ml of ethyl acetate, followed by washing with 100 ml of a saturated aqueous sodium hydrogen carbonate solution, 40 ml of water and 40 ml of a saturated aqueous sodium chloride solution in this order. The washed material was dried over anhydrous sodium sulfate and then subjected to vacuum distillation to remove the solvent, whereby was obtained 46.8 g (yield: 94.9%) of an oily title compound (diastereomixture). to give rise to a reaction by washing with 100 ml of a saturated aqueous sodium hydrogen carbonate solution, 40 ml of water and 40 ml of a saturated aqueous sodium chloride solution in this order The washed material was dried over anhydrous sodium sulfate subjected to vacuum distillation to remove the solvent

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

Procedure: 24.0 g of dehydrated isobutyl vinyl ether was dropwise added to a mixture of 32.7 g of isobutyl (R)-(+)-lactate and 0.3 g of phosphorus oxychloride which was being stirred at room temperature, so that the internal temperature of the reaction system could be kept at 40° C. or less. Then, the resulting mixture was stirred at room temperature overnight. After the reaction, thereto was added 200 ml of ethyl acetate, followed by washing with a saturated aqueous sodium hydrogen carbonate solution, water and a saturated aqueous sodium chloride solution in this order. The washed material was dried over anhydrous sodium sulfate and then subjected to vacuum distillation to remove the solvent. The resulting concentrate was subjected to distillation to obtain 47.8 g (yield: 96.9%) of an oily title compound (diastereomixture). could be kept at 40° C. or less Then, the resulting mixture was stirred at room temperature overnight After the reaction by washing with a saturated aqueous sodium hydrogen carbonate solution, water The washed material was dried over anhydrous sodium sulfate subjected to vacuum distillation to remove the solvent The resulting concentrate was subjected to distillation

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

Procedure: 17.2 g of dehydrated ethyl vinyl ether was dropwise added to a mixture of 32.7 g of isobutyl (R)-(+)-lactate and 0.3 g of phosphorus oxychloride which was being stirred at room temperature, so that the internal temperature of the reaction system could be kept at 40° C. or less. Then, the resulting mixture was stirred at room temperature overnight. After the reaction, thereto was added 200 ml of ethyl acetate, followed by washing with a saturated aqueous sodium hydrogen carbonate solution, water and a saturated aqueous sodium chloride solution in this order. The washed material was dried over anhydrous sodium sulfate and then subjected to vacuum distillation to remove the solvent. The resulting concentrate was subjected to distillation to obtain 40.1 g (yield: 91.8%) of an oily title compound (diastereomixture). could be kept at 40° C. or less Then, the resulting mixture was stirred at room temperature overnight After the reaction by washing with a saturated aqueous sodium hydrogen carbonate solution, water The washed material was dried over anhydrous sodium sulfate subjected to vacuum distillation to remove the solvent The resulting concentrate was subjected to distillation

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

Procedure: 21.8 g (0.26 mole) of 3,4-dihydro-2H-pyran was dropwise added at room temperature to a mixture of 29.2 g (0.2 mole) of isobutyl (R)-(+)-lactate and 0.3 g of phosphorus oxychloride. After the completion of the dropwise addition, the resulting mixture was stirred at room temperature for 4 hours. After the reaction, 100 ml of ethyl acetate was added, followed by washing with 70 ml of a saturated aqueous sodium hydrogen carbonate solution, 70 ml of water and 70 ml of a saturated aqueous sodium chloride solution in this order. The washed material was dried over anhydrous sodium sulfate and then subjected to vacuum distillation to remove the solvent, whereby was obtained 49.0 g (yield: 92.1%) of an oily title compound (diastereomixture). After the completion of the dropwise addition was added by washing with 70 ml of a saturated aqueous sodium hydrogen carbonate solution, 70 ml of water and 70 ml of a saturated aqueous sodium chloride solution in this order The washed material was dried over anhydrous sodium sulfate subjected to vacuum distillation to remove the solvent

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

Procedure: A mixture of isobutyl (R)-lactate (73 g, 0.5 mol, Merck) and 3,4-dihydro-2H-pyran (70 g, 0.83 mol, Merck) was treated with 5M hydrogen chloride in dimethylformamide (4 ml) and set aside at ambient temperature overnight in calcium chloride protected 250 ml round-bottom flask. Silver oxide (15 g) was added, the mixture stirred magnetically for 2 hours and then filtered. The product was isolated by distillation (13 Pa, b.p. 94-96° C.) to provide isobutyl 2-O-tetrahydropyranyl-(R)-lactate (102.5 g, 89%) as a colorless oil. filtered The product was isolated by distillation (13 Pa, b.p. 94-96° C.)