methyl 3,5-dichloro-4-hydroxybenzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 2 L, 3 necked, round bottom flask was charged with 2-aminoethanol (240 gm; 3.93 moles) and heated to 80° C. Methyl 3,5-dichloro-4-hydroxybenzoate (432 gm; 1.96 moles) was added in portions through a powder funnel. The resulting amber solution was heated to 145° C. and the liberated methanol distilled into a Dean Stark trap. The reaction required about 3.5 hrs. Upon completion, the solution was cooled to 90°-100° C. and dissolved in 1.95 L H2O. The aqueous solution was cooled to 25° C., placed in an ice bath and made slightly acidic with concentrated hydrochloric acid (196 ml; 2.35 moles). The product precipitated and filtration afforded a white solid. After drying at 50° C. in a vacuum oven, the product darkened slightly. The crude material (384.4 gm; 78.8%) was ground and passed through a No. 20 mesh screen to produce 3,5-dichloro-4-hydroxy-N-(2-hydroxyethyl)benzamide as a cream colored solid (m.p. 174°-178° C.) which is suitable for use in the next step. The resulting amber solution was heated to 145° C. the liberated methanol distilled into a Dean Stark trap The reaction required about 3.5 hrs Upon completion, the solution was cooled to 90°-100° C. The aqueous solution was cooled to 25° C. placed in an ice bath The product precipitated filtration afforded a white solid After drying at 50° C. in a vacuum oven

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

実験手順: To a stirred solution of methyl 3,5-dichloro-4-hydroxybenzoate (600 mg, 2.714 mmol), N-tert-butoxycarbonylprolinol (546 mg, 2.714 mmol), and Ph3P (854 mg, 3.257 mmol) in THF (10 mL) was added dropwise DIAD (0.68 mL, 3.283 mmol) at room temp and the mixture was stirred for 3 days at room temp, and for 18 hr at 70° C. The reaction mixture was concentrated and the residue was chromatographed on silica-gel with n-hexane-EtOAc (6:1, v/v) as eluent to give 988.8 mg (90%) methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3,5-dichlorobenzoate a pale yellowish oil. 1H-NMR (400 MHz, CDCl3) δ1.44 (s, 9H), 1.88-2.15 (br m, 3H), 2.34 (br s, 1H), 3.40-3.44 (m, 2H), 3.92 (s, 3H), 3.92, 4.14 (m, 1H), 4.18 (br s, 2H), 7.98 (s, 2H); MS (FAB) m/z 404 (M++1). for 18 hr at 70° C The reaction mixture was concentrated the residue was chromatographed on silica-gel with n-hexane-EtOAc (6:1

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

実験手順: To a stirred solution of methyl 3,5-dichloro-4-hydroxybenzoate (600 mg, 2.714 mmol), N-tert-butoxycarbonylprolinol (546 mg, 2.714 mmol), and Ph3P (854 mg, 3.257 mmol) in THF (10 mL) was added dropwise DIAD (0.68 mL, 3.283 mmol) at room temp and the mixture was stirred for 3 days at room temp, and for 18 hr at 70° C. The reaction mixture was concentrated and the residue was chromatographed on silica-gel with n-hexane-EtOAc (6:1, v/v) as eluent to give 988.8 mg (90%) methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3,5-dichlorobenzoate a pale yellowish oil. 1H-NMR (400 MHz, CDCl3) δ 1.44 (s, 9H), 1.88–2.15 (br m, 3H), 2.34 (br s, 1H), 3.40–3.44 (m, 2H), 3.92 (s, 3H), 3.92, 4.14 (m, 1H), 4.18 (br s, 2H), 7.98 (s, 2H); MS (FAB) m/z 404 (M++1). for 18 hr at 70° C The reaction mixture was concentrated the residue was chromatographed on silica-gel with n-hexane-EtOAc (6:1

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

実験手順: In a four-liter reaction vessel, 3 liters of methyl glycol (B.P. 122°-126° C.), 221 g (1 mole) of 3,5-dichloro-4-hydroxybenzoic acid methyl ester, 40 g (1 mole) of sodium hydroxide in 40 ml of water, and 289.8 g (0.5 mole) of 1,3-bis-(bromomethyl)-2,4,5,6-tetrabromobenzene were reacted and worked up in the manner described in Example 46. were reacted

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

実験手順: In a four-liter reaction vessel, 3 liters of methyl glycol (B.P. 122°-126° C.), 221 g (1 mole) of 3,5-dichloro-4-hydroxybenzoic acid methyl ester, 40 g (1 mole) of sodium hydroxide in 40 ml of water, and 289.8 g (0.5 mole) of 1,3-bis-(bromomethyl)-2,4,5,6-tetrabromobenzene were reacted and worked up in the manner described in Example 46. were reacted

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mechanically stirred mixture of 0.6 g of calcium acetate, 0.6 g of antimony oxide, 3.75 g (0.15 M) of 1,4-bis(3-hydroxy-2,2-dimethylpropyl)benzene and 132 g (0.6 M) of methyl 3,5-dichloro-4-hydroxybenzoate was heated under nitrogen atmosphere at 200° C. for 18 hours. The reaction mixture was washed three times with benzene in a Waring Blendor and extracted for 5 days with 2 liters of hot benzene. The extract, on cooling, yielded 70 g of 4,4'-[1,4-phenylenebis([2,2-dimethyl-1,3-propanediyl]oxycarbonyl)]bis(2,6-dichlorophenol) melting at 203°-204° C. The infrared spectrum was consistent with the indicated structure. The compound contained 3.185 meq. of OH/g indicating a molecular weight of 628 for the bisphenol. The reaction mixture was washed three times with benzene in a Waring Blendor extracted for 5 days with 2 liters of hot benzene The extract, on cooling

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mechanically stirred mixture of 0.6 g of calcium acetate, 0.6 g of antimony oxide, 15.7 g (0.15 M) of 2,2-dimethyl-1,3-propanediol, and 132 g (0.6 mole) of methyl 3,5-dichloro-4-hydroxybenzoate was heated under a nitrogen atmosphere at 200° C. for 18 hours. The reaction mixture was washed three times with benzene in a Waring Blendor and extracted for five days with 2 liters of hot benzene. The extract, on cooling, yielded 50.5 g of 4,4'-[2,2-dimethyl-1,3-propanediylbis(oxycarbonyl)]bis(2,6-dichlorophenol) melting at 180°-181° C. The infrared spectrum was consistent with the indicated structure. The compound contained 4.115 meq. of OH/g, indicating a molecular weight of 486 for the bisphenol. The reaction mixture was washed three times with benzene in a Waring Blendor extracted for five days with 2 liters of hot benzene The extract, on cooling

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

実験手順: A mixture of 3,5-dichloro-4-hydroxy benzoic acid methyl ester (5.525 g, 25 mmol), benzyl bromide (5.13 g, 30 mmol) and potassium carbonate (6.91 g, 50 mmol) in N,N-dimethylformamide (100 mL) was stirred overnight at room temperature. The reaction mixture was poured into crushed ice (ca. 300 g) and the product was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure. The solid residue was recrystallised from ethyl acetate and hexane. Yield: 7.47 g (96%) fine white needles. 1H-NMR (400 MHz, CDCl3) δ=3.93 (s, 3H, —OCH3), 5.12 (s, 2H, —CH2Ph), 7.35-7.44 (m, 3H), 7.54-7.58 (m, 2H), 8.01 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ=52.66, 75.12, 127.18, 128.41, 128.48, 129.79, 130.13, 135.57, 154.57, 164.39. The reaction mixture was poured the product was extracted with ethyl acetate (2×100 mL) The combined organic layers were dried over sodium sulphate concentrated under reduced pressure The solid residue was recrystallised from ethyl acetate and hexane

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

実験手順: Methyl 3,5-dichloro-4-hydroxybenzoate, (173, 0.78 mol), 1-bromododecane (234 g, 0.94 mol) and potassium carbonate (130 g, 0.94 g) in DMF (1000 mL) were heated to 70° C. with good stirring for about 8 hrs. The reaction was cooled and treated with 2N-HCl to neutralize the excess potassium carbonate. The mixture was then extracted with ethyl acetate. The ethyl acetate was washed with 2N-HCl(×3), dried (MgSO4), filtered and concentrated to give an oil. This oil was taken on to the next step without further purification. The reaction was cooled The mixture was then extracted with ethyl acetate The ethyl acetate was washed with 2N-HCl(×3) dried (MgSO4) filtered concentrated to give an oil This oil was taken on to the next step without further purification

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mechanically stirred mixture of 0.6 g of calcium acetate, 0.6 g of antimony oxide, 3.75 g (0.15 M) of 1,4-bis(3-hydroxy-2,2-dimethylpropyl)benzene and 132 g (0.6 M) of methyl 3,5-dichloro-4-hydroxybenzoate was heated under nitrogen atmosphere at 200° C for 18 hours. The reaction mixture was washed three times with benzene in a Waring Blendor and extracted for 5 days with 2 liters of hot benzene. The extract, on cooling, yielded 70 g of 4,4'-[1,4-phenylenebis([2,2-dimethyl-1,3-propanediyl]-oxycarbonyl)]bis(2,6-dichlorophenol) melting at 203°-204° C. The infrared spectrum was consistent with the indicated structure. The compound contained 3.185 meq. of OH/g indicating a molecular weight of 628 for the bisphenol. The reaction mixture was washed three times with benzene in a Waring Blendor extracted for 5 days with 2 liters of hot benzene The extract, on cooling

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mechanically stirred mixture of 0.6 g of calcium acetate, 0.6 g of antimony oxide, 3.75 g (0.15 M) of 1,4-bis(3-hydroxy-2,2-dimethylpropyl)benzene and 132 g (0.6 M) of methyl 3,5-dichloro-4-hydroxybenzoate was heated under nitrogen atmosphere at 200° C for 18 hours. The reaction mixture was washed three times with benzene in a Waring Blendor and extracted for 5 days with 2 liters of hot benzene. The extract, on cooling, yielded 70 g of 4,4'-[1,4-phenylenebis([2,2-dimethyl-1,3-propanediyl]-oxycarbonyl)]bis(2,6-dichlorophenol) melting at 203°-204° C. The infrared spectrum was consistent with the indicated structure. The compound contained 3.185 meq. of OH/g indicating a molecular weight of 628 for the bisphenol. The reaction mixture was washed three times with benzene in a Waring Blendor extracted for 5 days with 2 liters of hot benzene The extract, on cooling