1-bromo-4-(difluoromethyl)benzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-indole-3-carboxaldehyde obtained in Example 29-(1) and 1-bromo-4-difluoromethylbenzene were treated in a manner similar to Example 25-(2) to give crude 4-chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl 4-(difluoromethyl)phenyl methanol, which was used in the subsequent step without further purification.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-indole-3-carboxaldehyde obtained in Example 29-(1) and 1-bromo-4-difluoromethylbenzene were treated in a manner similar to Example 25-(2) to give crude 4-chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl 4-(difluoromethyl)phenyl methanol, which was used in the subsequent step without further purification.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of magnesium turnings (71 mg) in tetrahydrofuran (2 ml) was added dropwise a solution of 1-bromo-4-difluoromethylbenzene (587 mg) in tetrahydrofuran (1.5 ml) under being stirred vigorously. The mixture was warmed with a dryer, and thereto was added 1,2-dibromoethane (4 drops). The resultant mixture was vigorously stirred at room temperature till a disappearance of magnesium turnings, and then dropwise added to a solution of the above 4-fluoro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole-3-carboxaldehyde (350 mg) in tetrahydrofuran (4 ml) over 10 minutes at −78° C. under argon atmosphere. The mixture was stirred at same temperature for 1 hour, and thereto was added a saturated aqueous ammonium chloride solution (20 ml). The resultant mixture was extracted with ethyl acetate (50 ml) 3 times, and the combined organic layer was dried over magnesium sulfate. The insoluble materials were filtered off, and the filtrate was evaporated under reduced pressure to give crude 4-(difluoromethyl)phenyl 4-fluoro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl methanol, which was used in the subsequent step without further purification. The mixture was warmed with a dryer The mixture was stirred at same temperature for 1 hour The resultant mixture was extracted with ethyl acetate (50 ml) 3 times the combined organic layer was dried over magnesium sulfate The insoluble materials were filtered off the filtrate was evaporated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under exclusion of oxygen, a solution of 14.0 g (67.63 mmol) of 1-bromo-4-(difluoromethyl)benzene (CAS 51776-71-7) and 25.3 g (142 mmol) of N-bromosuccinimide (NBS) in 190 ml of carbon tetrachloride is irradiated using a daylight lamp. During the radiation, the solvent reaches its boiling point. The mixture is irradiated under reflux for 24 hours. The mixture is then allowed to cool to room temperature, and precipitated succinimide is filtered off. Another 25 g of NBS are added to the filtrate, and the mixture is once more, under exclusion of oxygen, irradiated under reflux for 24 hours. After cooling, the mixture is again filtered and the filtrate is evaporated to dryness. This gives 18 g of a dark orange oil which is purified by vacuum distillation at 13 torr. This gives 12.7 g (44.4 mmol, 66% yield) of a colorless oil. The mixture is irradiated under reflux for 24 hours precipitated succinimide is filtered off Another 25 g of NBS are added to the filtrate irradiated under reflux for 24 hours After cooling the mixture is again filtered the filtrate is evaporated to dryness This gives 18 g of a dark orange oil which is purified by vacuum distillation at 13 torr

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under exclusion of oxygen, a solution of 14.0 g (67.63 mmol) of 1-bromo-4-(difluoromethyl)benzene (CAS 51776-71-7) and 25.3 g (142 mmol) of N-bromosuccinimide (NBS) in 190 ml of carbon tetrachloride is irradiated using a daylight lamp. During the radiation, the solvent reaches its boiling point. The mixture is irradiated under reflux for 24 hours. The mixture is then allowed to cool to room temperature, and precipitated succinimide is filtered off. Another 25 g of NBS are added to the filtrate, and the mixture is once more, under exclusion of oxygen, irradiated under reflux for 24 hours. After cooling, the mixture is again filtered and the filtrate is evaporated to dryness. This gives 18 g of a dark orange oil which is purified by vacuum distillation at 13 torr. This gives 12.7 g (44.4 mmol, 66% yield) of a colorless oil. The mixture is irradiated under reflux for 24 hours precipitated succinimide is filtered off Another 25 g of NBS are added to the filtrate irradiated under reflux for 24 hours After cooling the mixture is again filtered the filtrate is evaporated to dryness This gives 18 g of a dark orange oil which is purified by vacuum distillation at 13 torr

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under exclusion of oxygen, a solution of 14.0 g (67.63 mmol) of 1-bromo-4-(difluoromethyl)benzene (CAS 51776-71-7) and 25.3 g (142 mmol) of N-bromosuccinimide (NBS) in 190 ml of carbon tetrachloride is irradiated using a daylight lamp. During the radiation, the solvent reaches its boiling point. The mixture is irradiated under reflux for 24 hours. The mixture is then allowed to cool to room temperature, and precipitated succinimide is filtered off. Another 25 g of NBS are added to the filtrate, and the mixture is once more, under exclusion of oxygen, irradiated under reflux for 24 hours. After cooling, the mixture is again filtered and the filtrate is evaporated to dryness. This gives 18 g of a dark orange oil which is purified by vacuum distillation at 13 torr. This gives 12.7 g (44.4 mmol, 66% yield) of a colorless oil. Boiling point (13 torr): 90-92° C. The mixture is irradiated under reflux for 24 hours precipitated succinimide is filtered off Another 25 g of NBS are added to the filtrate irradiated under reflux for 24 hours After cooling the mixture is again filtered the filtrate is evaporated to dryness This gives 18 g of a dark orange oil which is purified by vacuum distillation at 13 torr

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With exclusion of oxygen, a solution of 14.0 g (67.63 mmol) of 1-bromo-4-(difluoromethyl)benzene [CAS 51776-71-7] and 25.3 g (142 mmol) of N-bromosuccinimide (NBS) in 190 ml of tetrachloromethane is irradiated with a sun lamp. During this, the solvent reaches its boiling point. It is irradiated under reflux for 24 hours. The mixture is then allowed to cool to room temperature and precipitated succinimide is filtered off. The filtrate is again mixed with 25 g of NBS and irradiated once more with exclusion of oxygen under reflux for 24 hours. Cooling is followed by filtration again, and the filtrate is concentrated to dryness. 18 g of an orange-colored oil are obtained as crude product, which is purified further by vacuum distillation at 13 mmHg. 12.7 g (44.4 mmol, 66% yield) of a colorless oil are obtained. It is irradiated under reflux for 24 hours precipitated succinimide is filtered off The filtrate is again mixed with 25 g of NBS irradiated once more with exclusion of oxygen under reflux for 24 hours Cooling is followed by filtration again the filtrate is concentrated to dryness

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of ethyl 4-hydroxy-2-methyl-1-benzofuran-6-carboxylate (252c) (1.10 g, 5 mmol), 1-bromo-4-(difluoromethyl)benzene (1.24 g, 6 mmol), Cs2CO3 (2.44 g, 7.5 mmol) and CuI (5 mg, 0.03 mmol) in DMF (5 mL) was heated in a microwave at 160° C. for 60 minutes. Water was then added and the product was extracted with CHCl3 (3×), dried over MgSO4 and concentrated to give an oil residue. The oil was purified via silica gel chromatography using hexanes/EtOAc (100/0 to70/30) to give the title compound (710 mg, 41%) as a yellow solid. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.38 (t, J=7.06 Hz, 3 H) 2.44 (s, 3 H) 4.37 (q, J=7.06 Hz, 2 H) 6.22 (d, J=0.94 Hz, 1 H) 6.63 (t, J=56.61 Hz, 1 H) 7.03 (d, J=8.29 Hz, 2 H) 7.46 (d, J=8.29 Hz, 2 H) 7.55 (d, J=1.13 Hz, 1 H) 7.89-8.05 (m, 1 H). the product was extracted with CHCl3 (3×) dried over MgSO4 concentrated to give an oil residue The oil was purified via silica gel chromatography