4-bromo-1-(difluoromethyl)-2-fluorobenzene

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

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-cyclopentyl-2-propen-1-ol (34 g, 0.266 mol), 2-fluoro-4-bromo-difluoromethyl benzene, (40 g, 0.177 mol, 1.5 equiv), and NaHCO3 (17.8 g, 0.212 mol, 1.2 equiv) in anhydrous NMP (200 mL) was heated to 140° C. for 1 h, resulting in complete conversion by TLC. The reaction mixture was poured into water and extracted with CH2Cl2. The organic layer was separated, washed with brine and dried over anhydrous Na2SO4. After the removal of the solvent, the residue was purified by column chromatography using hexanes/ethyl acetate, and the product-containing fractions combined and concentrated. The residue was fractionally distilled through a Vigreux column to give 16 g (33%) of the desired product (bp 100° C./0.2 Torr). resulting in complete conversion by TLC extracted with CH2Cl2 The organic layer was separated washed with brine dried over anhydrous Na2SO4 After the removal of the solvent the residue was purified by column chromatography concentrated The residue was fractionally distilled through a Vigreux column

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-cyclopentyl-2-propen-1-ol (34 g, 0.266 mol), 2-fluoro-4-bromo-difluoromethyl benzene, (40 g, 0.177 mol, 1.5 equiv), and NaHCO3 (17.8 g, 0.212 mol, 1.2 equiv) in anhydrous NMP (200 mL) was heated to 140° C. for 1 h, resulting in complete conversion by TLC. The reaction mixture was poured into water and extracted with CH2Cl2. The organic layer was separated, washed with brine and dried over anhydrous Na2SO4. After the removal of the solvent, the residue was purified by column chromatography using hexanes/ethyl acetate, and the product-containing fractions combined and concentrated. The residue was fractionally distilled through a Vigreux column to give 16 g (33%) of the desired product (bp 100° C./0.2 Torr). 1H NMR (CDCl3) d 1.57 (m, 8H), 2.81 (m, 4H), 3.09 (m, 1H), 6.86 (t, 1H, J=57 Hz), 6.95 (m, 2H), 7.51 (t, 1H, J=7.5 Hz). MS (APCI) calcd for C15H17F3O, 270.29; found [M−19(−F)]: 251.02 m/z. resulting in complete conversion by TLC extracted with CH2Cl2 The organic layer was separated washed with brine dried over anhydrous Na2SO4 After the removal of the solvent the residue was purified by column chromatography concentrated The residue was fractionally distilled through a Vigreux column

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

Procedure: A mixture of 4-bromo-1-(difluoromethyl)-2-fluorobenzene (5.0 g, 22 mmol) and KCN (4.34 g, 67 mmol) was heated at 150° C. in NMP (50 mL) for 16 h. After trituration with a mixture of water, hexane, EtOAc and DCM, the organic layer was concentrated and purified by silica gel flash chromatography using hexanes:DCM (4:1 to 4:1.5 v/v) as mobile phase to yield the title compound: 1H NMR (500 MHz, CD2Cl2) δ 7.97 (s, 1H), 7.93 (d, J=8.5 Hz, 1H), 7.67 (d, J=8.5 Hz, 1H), 6.95 (t, J=54.5 Hz, 1H). the organic layer was concentrated purified by silica gel flash chromatography

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-cyclopentyl-2-propen-1-ol (34 g, 0.266 mol), 2-fluoro-4-bromo-difluoromethyl benzene, (40 g, 0.177 mol, 1.5 equiv), and NaHCO3 (17.8 g, 0.212 mol, 1.2 equiv) in anhydrous NMP (200 mL) was heated to 140° C. for 1 h, resulting in complete conversion by TLC. The reaction mixture was poured into water and extracted with CH2Cl2. The organic layer was separated, washed with brine and dried over anhydrous Na2SO4. After the removal of the solvent, the residue was purified by column chromatography using hexanes/ethyl acetate, and the product-containing fractions combined and concentrated. The residue was fractionally distilled through a Vigreux column to give 16 g (33%) of the desired product (bp 100° C./0.2 Torr). resulting in complete conversion by TLC extracted with CH2Cl2 The organic layer was separated washed with brine dried over anhydrous Na2SO4 After the removal of the solvent the residue was purified by column chromatography concentrated The residue was fractionally distilled through a Vigreux column