3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: In a round bottom flask, (0.9 g) 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid and (9.8 mg) p-toluene sulfonic acid and 2 ml toluene was taken. The reaction mixture was stirred at room temperature and subsequently 2 g (1 equiv) bis-(4-chlorophenyl)-dimethoxymethane [IIa4] diluted with 5 ml toluene was added through droping funnel. The reaction mixture was heated at reflux temperature and the water was removed azeotropically under Dean Stark. Continuous removal and addition of toluene was done up to 2 hrs. Then the reaction mixture was cooled at room temperature to obtain off white solid. It was filtered and washed with toluene and then water. was added The reaction mixture was heated at reflux temperature the water was removed azeotropically under Dean Stark Continuous removal and addition of toluene Then the reaction mixture was cooled at room temperature to obtain off white solid It was filtered washed with toluene

反応条件: temp:27.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a round bottom flask, (12 g) 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid and 35 ml toluene was taken. (99.4 mg) p-toluene sulfonic acid was added into the reaction mixture at 25-30° C. temperature. The reaction mixture was heated at reflux temperature, and 20.5 g (1 equiv.) dimethoxy diphenylmethane [IIa3] in 35 ml toluene was added and it was further refluxed under dean stark. Continuous removal and addition of toluene done upto 3 hrs. Then reaction mixture was cooled at 25-30° C. and dumped into water. The reaction mixture was stirred at 20-30° C. and filter it and wash the solid mass with water to obtain white solid product. The reaction mixture was heated was added it was further refluxed under dean stark Continuous removal and addition of toluene Then reaction mixture filter it wash the solid mass with water to obtain white solid product

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 435 g of benzaldehyde and 550 g 2,2-bis(hydroxymethyl)propanoic acid were allowed to react in the presence of a small amount of p-toluenesulphonic acid. The reaction was under stirring carried out at room temperature followed by heating to 40° C. under a low pressure (15 mm Hg). Yielded product was then dissolved in a mixture of 8000 ml aqueous sodium hydrogencarbonate (0.54M) and 2500 ml of diethyl ether. The aqueous phase was now washed with diethyl ether and acidified with 800 g of tartaric acid. The precipitate was collected and washed with water. Obtained product was finally recrystallized from ethanol/ethyl acetate to yield 745 g of 5-methyl-2-phenyl-1,3-dioxane-5-carboxylic acid. carried out at room temperature The aqueous phase was now washed with diethyl ether The precipitate was collected washed with water Obtained product was finally recrystallized from ethanol/ethyl acetate

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

実験手順: Synthesis of the acetal (formal) of formaldehyde and 2,2-bis(hydroxymethyl)propanoic acid yielding 5-methyl-1,3-dioxane-5-carboxylic acid.

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

実験手順: Synthesis of benzylidene protected 2,2-bis(hydroxymethyl)-propanoic acid, that is the acetal of benzaldehyde and 2,2-bis(hydroxymethyl)propanoic acid, yielding 5-methyl-2-phenyl-1,3-dioxane-5-carboxylic acid. Synthesis of benzylidene

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

実験手順: To a suspension of 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid (10.06 g, 75 mmol) in MeOH was dropped 2.0 M solution of (trimethylsilyl)diazomethane in diethyl ether and stirred at room temperature overnight. After solvent was concentrated under reduced pressure, the reaction was quenched with saturated NaHCO3 solution and extracted with CH2Cl2. Extracts were dried over MgSO4 and concentrated under reduced pressure to afford methyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate as an oil (3.79 g, 34%). 1H NMR (300 MHz, CDCl3) δ 3.81 (d, 2H), 3.67 (s, 3H), 3.60 (d, 2H), 2.89 (br, 2H), 0.96 (s, 3H). After solvent was concentrated under reduced pressure the reaction was quenched with saturated NaHCO3 solution extracted with CH2Cl2 Extracts were dried over MgSO4 concentrated under reduced pressure

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

実験手順: To a suspension of 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid (10.06 g, 75 mmol) in MeOH was dropped 2.0 M solution of (trimethylsilyl)diazomethane in diethyl ether and stirred at room temperature overnight. After solvent was concentrated under reduced pressure, the reaction was quenched with saturated NaHCO3 solution and extracted with CH2Cl2. Extracts were dried over MgSO4 and concentrated under reduced pressure to afford methyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate as an oil (3.79 g, 34%). 1H NMR (300 MHz, CDCl3) δ 3.81 (d, 2H), 3.67 (s, 3H), 3.60 (d, 2H), 2.89 (br, 2H), 0.96 (s, 3H). After solvent was concentrated under reduced pressure the reaction was quenched with saturated NaHCO3 solution extracted with CH2Cl2 Extracts were dried over MgSO4 concentrated under reduced pressure

反応条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: One loopful bacterial cells of Agrobacterium sp. SD807 strain were inoculated in 5 ml of a culture medium having the same composition as culture medium 2 shown in Table 3 and incubated with shaking at 30° C. for 1 day. After completion of the cultivation, the bacterial cells were harvested by centrifugation and a 50 mM potassium phosphate buffer solution containing 1,1,1-tris(hydroxymethyl)ethane in a concentration of 5 g/l was added thereto to prepare a resting cell suspension reaction mixture. This was shaken at 30° C. The reaction mixture had a turbidity in terms of absorbance of 0.2 at 660 nm. A portion of the reaction mixture was analyzed by high performance liquid chromatography and as a result, it was found that 4.9 g/l of 1,1,1-tris(hydroxymethyl)ethane had been oxidized at 66 hours of the reaction to produce 0.1 g/l of 2,2-bis (hydroxymethyl)propionaldehyde and 4.8 g/l of 2,2-bis (hydroxymethyl)propionic acid. Conversion rate of 1,1,1-tris(hydroxymethyl)ethane to 2,2-bis(hydroxymethyl)propionic acid was about 88%. was added to prepare a resting cell suspension reaction mixture This was shaken at 30° C had been oxidized at 66 hours of the reaction

反応条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: One loopful bacterial cells of Rhodococcus erythropolis SD806 strain were inoculated in 200 ml of a culture medium having the same composition as culture medium 1 shown in Table 3 and incubated with shaking at 30° C. for 2 days. After completion of the incubation, the bacterial cells were harvested by centrifugation and 1 liter of a 50 mM potassium phosphate buffer solution containing 5 g of 1,1,1-tris(hydroxymethyl)ethane was added thereto to prepare a resting cell suspension reaction mixture. The reaction mixture had a turbidity in terms of absorbance of 0.8 at 660 nm. This was shaken at 30° C. for 24 hours. A portion of the reaction mixture was analyzed by high performance liquid chromatography and as a result, it was found that 3.3 g of 1,1,1-tris(hydroxymethyl)ethane was oxidized and decomposed to produce 1.1 g of 2,2-bis (hydroxymethyl)propionaldehyde and 2.0 g of 2,2-bis (hydroxymethyl)propionic acid. was added to prepare a resting cell suspension reaction mixture This was shaken at 30° C. for 24 hours

反応条件: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: One loopful bacterial cells of Rhodococcus erythropolis SD806 strain were inoculated in 200 ml of a culture medium having the same composition as culture medium 1 shown in Table 3 and incubated with shaking at 30° C. for 2 days. After completion of the incubation, the bacterial cells were harvested by centrifugation and 1 liter of a 50 mM potassium phosphate buffer solution containing 5 g of 1,1,1-tris(hydroxymethyl)ethane was added thereto to prepare a resting cell suspension reaction mixture. The reaction mixture had a turbidity in terms of absorbance of 0.8 at 660 nm. This was shaken at 30° C. for 24 hours. A portion of the reaction mixture was analyzed by high performance liquid chromatography and as a result, it was found that 3.3 g of 1,1,1-tris(hydroxymethyl)ethane was oxidized and decomposed to produce 1.1 g of 2,2-bis (hydroxymethyl)propionaldehyde and 2.0 g of 2,2-bis (hydroxymethyl)propionic acid. was added to prepare a resting cell suspension reaction mixture This was shaken at 30° C. for 24 hours

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

実験手順: To a suspension of 2,2-bis(hydroxymethyl)propionic acid (131 g, 0.98 mole) in tetrahydrofuran (500 ml) was added a solution of phenylboronic acid (122 g, 1.0 mole) in tetrahydrofuran (500 ml). The mixture was stirred for 3 h and toluene (1.0 L) was added. Water was removed by azeotropic distillation with toluene. Heptanes (500 ml) was added to the precipitated product, heated to reflux and cooled. The mixture was filtered and washed with heptanes (2×300 ml). The solids were dried under vacuum at 70–75° C. until constant weight to give 94% yield. 1H NMR: δ (DMSO-d6) 7.65 (d, 2H, Ar), 7.40 (m, 3H, Ar), 4.35 (d, 2H, CH2), 3.92 (d, 2H, CH2), 1.17 (s, 3H, CH3) Water was removed by azeotropic distillation with toluene Heptanes (500 ml) was added to the precipitated product heated to reflux cooled The mixture was filtered washed with heptanes (2×300 ml) The solids were dried under vacuum at 70–75° C. until constant weight to give 94% yield