丙烷-1,1-二醇

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,6-Dibromobenzaldehyde (49) (10.0 g, 37.9 mmol) was dissolved in 160 ml dry CH2Cl2. Propanediol (6.4 ml, 88.5 ml), triethylorthoformate (6.83 ml, 41 mmol) and anhydrous ZrCl4 (1.0 g) were added at ambient temperature and stirred overnight. Then NaOH (50 ml of a 10% solution) was added and stirred for an additional hour. The organic phase was separated, the aqueous phase was extracted with Et2O (2×40 ml). The combined organic phases were washed with water (3×60 ml), dried over MgSO4 and the volatiles were removed in vacuo to afford 12 g (98%) 2-(2,6-Dibromophenyl)-1,3-dioxane (acetal) as a slightly yellow solid. stirred for an additional hour The organic phase was separated the aqueous phase was extracted with Et2O (2×40 ml) The combined organic phases were washed with water (3×60 ml) dried over MgSO4 the volatiles were removed in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Compound 18 was synthesized as described above for compound 10 from (S)-(+)-3-benzoyl-α-methylbenzeneacetic acid (ketoprofen, 17) (3.8 g, 15 mmol) and propanediol (9) (5.7 g, 75 mmol). The compound was purified by flash chromatography on a silica gel column using 200:1 CH2Cl2—MeOH as the eluent to give 2.63 g (56%) of the compound 18 as a colorless oil; 1H NMR (CDCl3) δ1.54 (d, 3H), 1.82 (m, 2H), 1.82-1.82 (b, 1H, ex D2O), 3.58 (m, 2H), 3.79-3.83 (q, 1H), 4.25 (m, 2H), 7.42-7.80 (m, 9H); MS (ES) m/z 313.1 (M+H)+ (C19H21O4 requires 313.3). Compound 18 was synthesized The compound was purified by flash chromatography on a silica gel column

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Compound 18 was synthesized as described above for compound 10 from (S)-(+)-3-benzoyl-α-methylbenzeneacetic acid (ketoprofen, 17) (3.8 g, 15 mmol) and propanediol (9) (5.7 g, 75 mmol). The compound was purified by flash chromatography on a silica gel column using 200:1 CH2Cl2—MeOH as the eluent to give 2.63 g (56%) of the compound 18 as a colorless oil; 1H NMR (CDCl3) δ1.54 (d, 3H), 1.82 (m, 2H), 1.82-1.82 (b, 1H, ex D2O), 3.58 (m, 2H), 3.79-3.83 (q, 1H), 4.25 (m, 2H), 7.42-7.80 (m, 9H); MS (ES) m/z 313.1 (M+H)+ (C19H21O4 requires 313.3). Compound 18 was synthesized The compound was purified by flash chromatography on a silica gel column

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Acetic acid [(3,5-bis-chlorocarbonyl-2,4,6-triiodo-phenyl)-methyl-carbamoyl]-methyl ester (16.25 g, 22.9 mmol) and 3-methylamino-1,2,-propanediol (4.42 ml, 45.8 mmol) were stirred in DMA (80 ml) for 72 hours at room temperature. The mixture was diluted with ethyl acetate (150 ml) and washed with ice water/brine (50:50, 20 ml×3). The organics were collected, dried over MgSO4, filtered and evaporated to dryness. The product was purified by silica column chromatography eluting with DCM: methanol to give acetic acid ({3-chlorocarbonyl-5-[(2,3-dihydroxy-propyl)-methyl-carbamoyl]-2,4,6-triiodo-phenyl}-methyl-carbamoyl)-methyl ester (5.42 g, 6.96 mmol). washed with ice water/brine (50:50, 20 ml×3) The organics were collected dried over MgSO4 filtered evaporated to dryness The product was purified by silica column chromatography eluting with DCM

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 25.5 ml of propane diol are slowly added dropwise at RT to a suspension of 3.37 g of sodium hydride (60% by weight in mineral oil) in 400 ml of DMF. After gas evolution ceases, 20 g of tert-butyl 2-bromomethyl-6-methylbenzoate are added, and the solution is stirred at RT for 72 h. Water is added and the solution is extracted twice with MTBE, and the org. phases are combined, washed with water and sat. NaCl solution, dried over MgSO4 and concentrated. The residue is chromatographed on silica gel with a heptane/ethyl acetate gradient, resulting in 16 g of tert-butyl 2-(3-hydroxypropoxymethyl)-6-methylbenzoate as a colorless oil. the solution is extracted twice with MTBE washed with water and sat. NaCl solution dried over MgSO4 concentrated The residue is chromatographed on silica gel with a heptane/ethyl acetate gradient resulting in 16 g of tert-butyl 2-(3-hydroxypropoxymethyl)-6-methylbenzoate as a colorless oil

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Acetic acid [(3,5-bis-chlorocarbonyl-2,4,6-triiodo-phenyl)-methyl-carbamoyl]-methyl ester (16.25 g, 22.9 mmol) and 3-methylamino-1,2,-propanediol (4.42 ml, 45.8 mmol) were stirred in DMA (80 ml) for 72 hours at room temperature. The mixture was diluted with ethyl acetate (150 ml) and washed with ice water/brine (50:50, 20 ml×3). The organics were collected, dried over MgSO4, filtered and evaporated to dryness. The product was purified by silica column chromatography eluting with DCM: methanol to give acetic acid ({3-chlorocarbonyl-5-[(2,3-dihydroxy-propyl)-methyl-carbamoyl]-2,4,6-triiodo-phenyl}-methyl-carbamoyl)-methyl ester (5.42 g, 6.96 mmol). washed with ice water/brine (50:50, 20 ml×3) The organics were collected dried over MgSO4 filtered evaporated to dryness The product was purified by silica column chromatography eluting with DCM

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 25.5 ml of propane diol are slowly added dropwise at RT to a suspension of 3.37 g of sodium hydride (60% by weight in mineral oil) in 400 ml of DMF. After gas evolution ceases, 20 g of tert-butyl 2-bromomethyl-6-methylbenzoate are added, and the solution is stirred at RT for 72 h. Water is added and the solution is extracted twice with MTBE, and the org. phases are combined, washed with water and sat. NaCl solution, dried over MgSO4 and concentrated. The residue is chromatographed on silica gel with a heptane/ethyl acetate gradient, resulting in 16 g of tert-butyl 2-(3-hydroxypropoxymethyl)-6-methylbenzoate as a colorless oil. the solution is extracted twice with MTBE washed with water and sat. NaCl solution dried over MgSO4 concentrated The residue is chromatographed on silica gel with a heptane/ethyl acetate gradient resulting in 16 g of tert-butyl 2-(3-hydroxypropoxymethyl)-6-methylbenzoate as a colorless oil

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,6-Dibromobenzaldehyde (49) (10.0 g, 37.9 mmol) was dissolved in 160 ml dry CH2Cl2. Propanediol (6.4 ml, 88.5 ml), triethylorthoformate (6.83 ml, 41 mmol) and anhydrous ZrCl4 (1.0 g) were added at ambient temperature and stirred overnight. Then NaOH (50 ml of a 10% solution) was added and stirred for an additional hour. The organic phase was separated, the aqueous phase was extracted with Et2O (2×40 ml). The combined organic phases were washed with water (3×60 ml), dried over MgSO4 and the volatiles were removed in vacuo to afford 12 g (98%) 2-(2,6-Dibromophenyl)-1,3-dioxane (acetal) as a slightly yellow solid. stirred for an additional hour The organic phase was separated the aqueous phase was extracted with Et2O (2×40 ml) The combined organic phases were washed with water (3×60 ml) dried over MgSO4 the volatiles were removed in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Acetic acid [(3,5-bis-chlorocarbonyl-2,4,6-triiodo-phenyl)-methyl-carbamoyl]-methyl ester (16.25 g, 22.9 mmol) and 3-methylamino-1,2,-propanediol (4.42 ml, 45.8 mmol) were stirred in DMA (80 ml) for 72 hours at room temperature. The mixture was diluted with ethyl acetate (150 ml) and washed with ice water/brine (50:50, 20 ml×3). The organics were collected, dried over MgSO4, filtered and evaporated to dryness. The product was purified by silica column chromatography eluting with DCM: methanol to give acetic acid ({3-chlorocarbonyl-5-[(2,3-dihydroxy-propyl)-methyl-carbamoyl]-2,4,6-triiodo-phenyl}-methyl-carbamoyl)-methyl ester (5.42 g, 6.96 mmol). washed with ice water/brine (50:50, 20 ml×3) The organics were collected dried over MgSO4 filtered evaporated to dryness The product was purified by silica column chromatography eluting with DCM

反应条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Propanediol (0.3 mole) is cooled under a nitrogen atmosphere to a temperature of 0° C. Then 4-bromo-3,5-difluorophenylbenzoylchloride (0.3 mole) are swiftly added with continuous stirring. The reaction mixture is then cooled to −10° C. and triflic acid (0.45 mole) is added. The reaction mixture is stirred further for 1 hour, then acetic anhydride (2 mole) is added maintaining the temperature below 5° C. After adding diethyl ether and stirring for 1 more hour at −10° C., 4-bromo-3,5-difluorophenyl-thianylium triflate is filtered off and washed with cold ether. maintaining the temperature below 5° C stirring for 1 more hour at −10° C. 4-bromo-3,5-difluorophenyl-thianylium triflate is filtered off washed with cold ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,6-Dibromobenzaldehyde (49) (10.0 g, 37.9 mmol) was dissolved in 160 ml dry CH2Cl2. Propanediol (6.4 ml, 88.5 ml), triethylorthoformate (6.83 ml, 41 mmol) and anhydrous ZrCl4 (1.0 g) were added at ambient temperature and stirred overnight. Then NaOH (50 ml of a 10% solution) was added and stirred for an additional hour. The organic phase was separated, the aqueous phase was extracted with Et2O (2×40 ml). The combined organic phases were washed with water (3×60 ml), dried over MgSO4 and the volatiles were removed in vacuo to afford 12 g (98%) 2-(2,6-Dibromophenyl)-1,3-dioxane (acetal) as a slightly yellow solid. stirred for an additional hour The organic phase was separated the aqueous phase was extracted with Et2O (2×40 ml) The combined organic phases were washed with water (3×60 ml) dried over MgSO4 the volatiles were removed in vacuo

反应条件: temp:175.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution containing 2 mls 1,3-propanediol, 15 mls water, 3 mls of 57% hydriodic acid and 0.1 g RhCl3.XH2O were placed in an autoclave, pressurized with 1200 psi of carbon monoxide, and heated with shaking at 175° C. for 6 hours. Analysis indicated the presence of 7.8 millimoles of gamma-butyrolactones (28.2% conversion based on the propanediol introduced). Unreacted propanediol and 3-hydroxypropyliodide were also present. The solution was returned to the autoclave, pressurized with 1100 psi of carbon monoxide and heated with shaking at 175° C. for 6 hours more. The product now contained 15.1 millimoles of gamma-butyrolactone (54.4% conversion), but some 3-hydroxypropyliodide was also present. No glutaric acid was formed. heated introduced) heated with shaking at 175° C. for 6 hours more