乙烯环己醇

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A distillation column-provided four-necked flask having a volume of one liter, which was equipped with a dropping funnel, a thermometer, a stirring device and a reflux ratio regulator, was charged with 250 g (1.922 moles) of 1-vinyl-1-cyclohexanol, 415.6 g (3.843 moles) of trimethyl orthoacetate and 1.4 g (0.019 moles) of propionic acid, and the internal temperature was raised to 115° C. Heating was continued for 12 hours while removing a fraction of not higher than 65° C. from a column top of the distillation column. After confirming the disappearance of 1-vinyl-1-cyclohexanol by a gas chromatographic analysis of the reaction solution, the reaction solution was distilled in vacuo. Fractions of from 120 to 130° C./1.2 kPa were collected to obtain 301.2 g (1.653 moles) of methyl 4-cyclohexylidenebutanoate. The yield was 86.0%. A distillation column-provided four-necked flask was equipped with a dropping funnel Heating while removing a fraction of not higher than 65° C. from a column top of the distillation column the reaction solution was distilled in vacuo Fractions of from 120 to 130° C./1.2 kPa were collected

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-(3-(3-bromo-5-fluorophenyl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide (0.58 g, 1.57 mmol), 1-vinylcyclohexanol (0.3 g, 2.38 mmol) and palladium acetate (0.03 g, 0.12 mmol) in tetrabutyl ammonium acetate (1.0 g) and DMF (1 ml) was heated at 90° C. for 1 h. After cooled to room temperature, the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml). Ethyl acetate portion was dried over Na2SO4. Purification by chromatography (40 to 60% EtOAc-hexanes gradient) gave (E)-2,2,2-trifluoro-N-(3-(3-fluoro-5-(2-(1-hydroxycyclohexyl)vinyl)phenyl)-3-hydroxypropyl)acetamide as a colorless oil. Yield (0.25 g, 54%): H NMR (400 MHz, DMSO-d6) δ 9.32 (t, J=5.6 Hz, 1H), 6.94-7.18 (m, 3H), 6.41-6.53 (m, 2H), 5.42 (d, J=4.4 Hz, 1H), 4.54-4.60 (m, 1H), 3.18-3.26 (m, 2H), 1.72-1.86 (m, 2H), 1.38-1.66 (m, 10H). After cooled to room temperature the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml) Ethyl acetate portion was dried over Na2SO4 Purification by chromatography (40 to 60% EtOAc-hexanes gradient)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-(3-(3-bromo-5-fluorophenyl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide (0.58 g, 1.57 mmol), 1-vinylcyclohexanol (0.3 g, 2.38 mmol) and palladium acetate (0.03 g, 0.12 mmol) in tetrabutyl ammonium acetate (1.0 g) and DMF (1 ml) was heated at 90° C. for 1 h. After cooled to room temperature, the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml). Ethyl acetate portion was dried over Na2SO4. Purification by chromatography (40 to 60% EtOAc-hexanes gradient) gave (E)-2,2,2-trifluoro-N-(3-(3-fluoro-5-(2-(1-hydroxycyclohexyl)vinyl)phenyl)-3-hydroxypropyl)acetamide as a colorless oil. Yield (0.25 g, 54%): H NMR (400 MHz, DMSO-d6) δ 9.32 (t, J=5.6 Hz, 1H), 6.94-7.18 (m, 3H), 6.41-6.53 (m, 2H), 5.42 (d, J=4.4 Hz, 1H), 4.54-4.60 (m, 1H), 3.18-3.26 (m, 2H), 1.72-1.86 (m, 2H), 1.38-1.66 (m, 10H). After cooled to room temperature the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml) Ethyl acetate portion was dried over Na2SO4 Purification by chromatography (40 to 60% EtOAc-hexanes gradient)

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

实验步骤: The title compound is prepared from 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one and 1-vinyl-cyclohexanol analogous to Example 44: (M−1)−=353; HPLC retention time=1.35 min (method A).

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

实验步骤: The title compound is prepared from 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one and 1-vinyl-cyclohexanol analogous to Example 44: (M−1)−=353; HPLC retention time=1.35 min (method A).

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-(3-(3-bromo-5-fluorophenyl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide (0.58 g, 1.57 mmol), 1-vinylcyclohexanol (0.3 g, 2.38 mmol) and palladium acetate (0.03 g, 0.12 mmol) in tetrabutyl ammonium acetate (1.0 g) and DMF (1 ml) was heated at 90° C. for 1 h. After cooled to room temperature, the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml). Ethyl acetate portion was dried over Na2SO4. Purification by chromatography (40 to 60% EtOAc-hexanes gradient) gave (E)-2,2,2-trifluoro-N-(3-(3-fluoro-5-(2-(1-hydroxycyclohexyl)vinyl)phenyl)-3-hydroxypropyl)acetamide as a colorless oil. Yield (0.25 g, 54%): 1H NMR (400 MHz, DMSO-d6) δ 9.32 (t, J=5.6 Hz, 1H), 6.94-7.18 (m, 3H), 6.41-6.53 (m, 2H), 5.42 (d, J=4.4 Hz, 1H), 4.54-4.60 (m, 1H), 3.18-3.26 (m, 2H), 1.72-1.86 (m, 2H), 1.38-1.66 (m, 10H). After cooled to room temperature the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml) Ethyl acetate portion was dried over Na2SO4 Purification by chromatography (40 to 60% EtOAc-hexanes gradient)

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A distillation column-provided four-necked flask having a volume of one liter, which was equipped with a dropping funnel, a thermometer, a stirring device and a reflux ratio regulator, was charged with 250 g (1.922 moles) of 1-vinyl-1-cyclohexanol, 415.6 g (3.843 moles) of trimethyl orthoacetate and 1.4 g (0.019 moles) of propionic acid, and the internal temperature was raised to 115° C. Heating was continued for 12 hours while removing a fraction of not higher than 65° C. from a column top of the distillation column. After confirming the disappearance of 1-vinyl-1-cyclohexanol by a gas chromatographic analysis of the reaction solution, the reaction solution was distilled in vacuo. Fractions of from 120 to 130° C./1.2 kPa were collected to obtain 301.2 g (1.653 moles) of methyl 4-cyclohexylidenebutanoate. The yield was 86.0%. A distillation column-provided four-necked flask was equipped with a dropping funnel Heating while removing a fraction of not higher than 65° C. from a column top of the distillation column the reaction solution was distilled in vacuo Fractions of from 120 to 130° C./1.2 kPa were collected

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A distillation column-provided four-necked flask having a volume of one liter, which was equipped with a dropping funnel, a thermometer, a stirring device and a reflux ratio regulator, was charged with 250 g (1.922 moles) of 1-vinyl-1-cyclohexanol, 415.6 g (3.843 moles) of trimethyl orthoacetate and 1.4 g (0.019 moles) of propionic acid, and the internal temperature was raised to 115° C. Heating was continued for 12 hours while removing a fraction of not higher than 65° C. from a column top of the distillation column. After confirming the disappearance of 1-vinyl-1-cyclohexanol by a gas chromatographic analysis of the reaction solution, the reaction solution was distilled in vacuo. Fractions of from 120 to 130° C./1.2 kPa were collected to obtain 301.2 g (1.653 moles) of methyl 4-cyclohexylidenebutanoate. The yield was 86.0%. A distillation column-provided four-necked flask was equipped with a dropping funnel Heating while removing a fraction of not higher than 65° C. from a column top of the distillation column the reaction solution was distilled in vacuo Fractions of from 120 to 130° C./1.2 kPa were collected

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A distillation column-provided four-necked flask having a volume of one liter, which was equipped with a dropping funnel, a thermometer, a stirring device and a reflux ratio regulator, was charged with 250 g (1.922 moles) of 1-vinyl-1-cyclohexanol, 415.6 g (3.843 moles) of trimethyl orthoacetate and 1.4 g (0.019 moles) of propionic acid, and the internal temperature was raised to 115° C. Heating was continued for 12 hours while removing a fraction of not higher than 65° C. from a column top of the distillation column. After confirming the disappearance of 1-vinyl-1-cyclohexanol by a gas chromatographic analysis of the reaction solution, the reaction solution was distilled in vacuo. Fractions of from 120 to 130° C./1.2 kPa were collected to obtain 301.2 g (1.653 moles) of methyl 4-cyclohexylidenebutanoate. The yield was 86.0%. A distillation column-provided four-necked flask was equipped with a dropping funnel Heating while removing a fraction of not higher than 65° C. from a column top of the distillation column the reaction solution was distilled in vacuo Fractions of from 120 to 130° C./1.2 kPa were collected

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A distillation column-provided four-necked flask having a volume of one liter, which was equipped with a dropping funnel, a thermometer, a stirring device and a reflux ratio regulator, was charged with 250 g (1.922 moles) of 1-vinyl-1-cyclohexanol, 415.6 g (3.843 moles) of trimethyl orthoacetate and 1.4 g (0.019 moles) of propionic acid, and the internal temperature was raised to 115° C. Heating was continued for 12 hours while removing a fraction of not higher than 65° C. from a column top of the distillation column. After confirming the disappearance of 1-vinyl-1-cyclohexanol by a gas chromatographic analysis of the reaction solution, the reaction solution was distilled in vacuo. Fractions of from 120 to 130° C./1.2 kPa were collected to obtain 301.2 g (1.653 moles) of methyl 4-cyclohexylidenebutanoate. The yield was 86.0%. A distillation column-provided four-necked flask was equipped with a dropping funnel Heating while removing a fraction of not higher than 65° C. from a column top of the distillation column the reaction solution was distilled in vacuo Fractions of from 120 to 130° C./1.2 kPa were collected

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-(3-(3-bromo-5-fluorophenyl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide (0.58 g, 1.57 mmol), 1-vinylcyclohexanol (0.3 g, 2.38 mmol) and palladium acetate (0.03 g, 0.12 mmol) in tetrabutyl ammonium acetate (1.0 g) and DMF (1 ml) was heated at 90° C. for 1 h. After cooled to room temperature, the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml). Ethyl acetate portion was dried over Na2SO4. Purification by chromatography (40 to 60% EtOAc-hexanes gradient) gave (E)-2,2,2-trifluoro-N-(3-(3-fluoro-5-(2-(1-hydroxycyclohexyl)vinyl)phenyl)-3-hydroxypropyl)acetamide as a colorless oil. Yield (0.25 g, 54%): H NMR (400 MHz, DMSO-d6) δ 9.32 (t, J=5.6 Hz, 1H), 6.94-7.18 (m, 3H), 6.41-6.53 (m, 2H), 5.42 (d, J=4.4 Hz, 1H), 4.54-4.60 (m, 1H), 3.18-3.26 (m, 2H), 1.72-1.86 (m, 2H), 1.38-1.66 (m, 10H). After cooled to room temperature the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml) Ethyl acetate portion was dried over Na2SO4 Purification by chromatography (40 to 60% EtOAc-hexanes gradient)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of N-(3-(3-bromo-5-fluorophenyl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide (0.58 g, 1.57 mmol), 1-vinylcyclohexanol (0.3 g, 2.38 mmol) and palladium acetate (0.03 g, 0.12 mmol) in tetrabutyl ammonium acetate (1.0 g) and DMF (1 ml) was heated at 90° C. for 1 h. After cooled to room temperature, the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml). Ethyl acetate portion was dried over Na2SO4 Purification by chromatography (40 to 60% EtOAc-hexanes gradient) gave (E)-2,2,2-trifluoro-N-(3-(3-fluoro-5-(2-(1-hydroxycyclohexyl)vinyl)phenyl)-3-hydroxypropyl)acetamide as a colorless oil. Yield (0.25 g, 54%): 1H NMR (400 MHz, DMSO-d6) δ 9.32 (t, J=5.6 Hz, 1H), 6.94-7.18 (m, 3H), 6.41-6.53 (m, 2H), 5.42 (d, J=4.4 Hz, 1H), 4.54-4.60 (m, 1H), 3.18-3.26 (m, 2H), 1.72-1.86 (m, 2H), 1.38-1.66 (m, 10H). After cooled to room temperature the reaction mixture was partitioned between water (40 ml) and ethyl acetate (60 ml) Ethyl acetate portion was dried over Na2SO4 Purification by chromatography (40 to 60% EtOAc-hexanes gradient)