2,3-二氟-4-甲基苯酚

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 0.023 g (0.10 mmol) (S)—N-{1-[4-(3-hydroxy-azetidin-1-yl)-phenyl]-ethyl}-acetamide (V.1) in 5 mL THF are added 0.017 mL (0.12 mmol) TEA and the mixture is cooled to 0° C. 0.008 mL (0.10 mmol) methanesulfonyl chloride are added dropwise and the mixture is stirred for 2 h at 0° C. Water is added and the aq. phase is extracted with ethyl acetate (2×). The combined organic layers are dried (MgSO4) and concentrated. The residue is taken up in 1.0 mL DMA and is added to a mixture of 0.014 g (0.12 mmol) 2,3-difluoro-4-methylphenol and 0.039 g (0.12 mmol) Cs2CO3 in 1.0 mL DMA. The resulting mixture is stirred for 12 h at 100° C. After cooling the mixture is directly purified by HPLC (MeOH/water (+0.1% NH4OH)) to yield the desired product. the aq. phase is extracted with ethyl acetate (2×) The combined organic layers are dried (MgSO4) concentrated The resulting mixture is stirred for 12 h at 100° C After cooling the mixture is directly purified by HPLC (MeOH/water (+0.1% NH4OH))

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 0.023 g (0.10 mmol) (S)—N-{1-[4-(3-hydroxy-azetidin-1-yl)-phenyl]-ethyl}-acetamide (V.1) in 5 mL THF are added 0.017 mL (0.12 mmol) TEA and the mixture is cooled to 0° C. 0.008 mL (0.10 mmol) methanesulfonyl chloride are added dropwise and the mixture is stirred for 2 h at 0° C. Water is added and the aq. phase is extracted with ethyl acetate (2×). The combined organic layers are dried (MgSO4) and concentrated. The residue is taken up in 1.0 mL DMA and is added to a mixture of 0.014 g (0.12 mmol) 2,3-difluoro-4-methylphenol and 0.039 g (0.12 mmol) Cs2CO3 in 1.0 mL DMA. The resulting mixture is stirred for 12 h at 100° C. After cooling the mixture is directly purified by HPLC (MeOH/water (+0.1% NH4OH)) to yield the desired product. the aq. phase is extracted with ethyl acetate (2×) The combined organic layers are dried (MgSO4) concentrated The resulting mixture is stirred for 12 h at 100° C After cooling the mixture is directly purified by HPLC (MeOH/water (+0.1% NH4OH))

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 0.023 g (0.10 mmol) (S)—N-{1-[4-(3-hydroxy-azetidin-1-yl)-phenyl]-ethyl}-acetamide (V.1) in 5 mL THF are added 0.017 mL (0.12 mmol) TEA and the mixture is cooled to 0° C. 0.008 mL (0.10 mmol) methanesulfonyl chloride are added dropwise and the mixture is stirred for 2 h at 0° C. Water is added and the aq. phase is extracted with ethyl acetate (2×). The combined organic layers are dried (MgSO4) and concentrated. The residue is taken up in 1.0 mL DMA and is added to a mixture of 0.014 g (0.12 mmol) 2,3-difluoro-4-methylphenol and 0.039 g (0.12 mmol) Cs2CO3 in 1.0 mL DMA. The resulting mixture is stirred for 12 h at 100° C. After cooling the mixture is directly purified by HPLC (MeOH/water (+0.1% NH4OH)) to yield the desired product. the aq. phase is extracted with ethyl acetate (2×) The combined organic layers are dried (MgSO4) concentrated The resulting mixture is stirred for 12 h at 100° C After cooling the mixture is directly purified by HPLC (MeOH/water (+0.1% NH4OH))

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

实验步骤: A solution of 2,3-difluoro-4-methyl phenol (3.3 g, 22.89 mmol) in THF (30 ml) was cooled to 0° C. in an ice bath, and 60% NaH (0.916 g, 22.9 mmol) was added. When the gas evolution ceased, methyl chloroformate (1.76 ml, 22.9 mmol) was added. The ice-bath was removed and the mixture was stirred at room temperature for three hours. Water was added and the mixture was extracted with EtOAc. The combined extracts were washed with water and brine, dried over MgSO4, filtered and concentrated to dryness under reduced pressure. Purification of the crude product by flash chromatography (hexanes:EtOAc 9:1) gave 3.85 g (83%) of carbonic acid 2,3-difluoro-4-methyl-phenyl ester methyl ester as a clear oil. The ice-bath was removed Water was added the mixture was extracted with EtOAc The combined extracts were washed with water and brine dried over MgSO4 filtered concentrated to dryness under reduced pressure Purification of the crude product by flash chromatography (hexanes:EtOAc 9:1)

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

实验步骤: To 2,3-difluoro-4-methylphenol (1 g, 6.94 mmol) in dichloromethane at 0° C. was added nitric acid 70% (0.7 mL, 7.77 mmol). After 1 h at room temperature the solution was washed with water, dried and evaporated to give 2,3-difluoro-4-methyl-6-nitrophenol (1.2 g, 6.35 mmol, 91% yield) (D44) as yellow solid. After 1 h at room temperature the solution was washed with water dried evaporated

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

实验步骤: To 2,3-difluoro-4-methylphenol (1 g, 6.94 mmol) in dichloromethane at 0° C. was added nitric acid 70% (0.7 mL, 7.77 mmol). After 1 h at room temperature the solution was washed with water, dried and evaporated to give 2,3-difluoro-4-methyl-6-nitrophenol (1.2 g, 6.35 mmol, 91% yield) (D44) as yellow solid. After 1 h at room temperature the solution was washed with water dried evaporated