1-(2-chloroethyl)-4-fluorobenzene

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:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cool a solution of N-(1,1-dimethylethyl)-3-methyl-2-pyridinecarboxamide in dry THF to -40° C. and add 2 equivalents of n-butyl lithium. Add a large excess of sodium bromide and stir for 15 minutes. Add 1 eq. of 4-fluorophenethyl chloride and stir for 2.5 hours while warming to -5° C. Quench the reaction with water and extract the product twice with ethyl acetate, then wash with brine (2X). Dry the organic phase over Na2SO4, filter and remove the solvent to produce the title compound. stir for 2.5 hours Quench the reaction with water extract the product twice with ethyl acetate wash with brine (2X) Dry the organic phase over Na2SO4 filter remove the solvent

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cool a solution of N-(1,1-dimethylethyl)-3-methyl-2-pyridinecarboxamide in dry THF to -40° C. and add 2 equivalents of n-butyl lithium. Add a large excess of sodium bromide and stir for 15 minutes. Add 1 eq. of 4-fluorophenethyl chloride and stir for 2.5 hours while warming to -5° C. Quench the reaction with water and extract the product twice with ethyl acetate, then wash with brine (2X). Dry the organic phase over Na2SO4, filter and remove the solvent to produce the title compound. stir for 2.5 hours Quench the reaction with water extract the product twice with ethyl acetate wash with brine (2X) Dry the organic phase over Na2SO4 filter remove the solvent

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: piperazinone (1.20 g, 12.1 mmol), 1-fluoro-4-(2-chloroethyl)benzene (2.45 g, 12.1 mmol) and i-Pr2NEt (3.25 g, 4.5 ml, 25 mmol) were combined in acetonitrile (25 mL) and heated to 85° C. for 2 h. The mixture was concentrated and partitioned between H2O (20 mL) and CH2Cl2 (20 mL), and the organic layer was removed. The aqueous layer was extracted with CH2Cl2 (3×20 mL), the combined organics were concentrated, and the residue was dissolved in 2 N HCl (50 mL). This acidic mixture was washed with CH2Cl2 (3×20 mL) and then made basic with 6 N NaOH. The basic mixture was extracted with CH2Cl2 (3×20 mL), and the extracts were combined, dried and concentrated to provide the title compound (1.30 g, 48%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.18-7.13 (m, 2H), 7.00-6.94 (m, 2H), 6.45 (s, 1H), 3.39-3.35 (m, 2H), 3.20 (s, 2H), 2.78-2.62 (m, 6H). The mixture was concentrated partitioned between H2O (20 mL) and CH2Cl2 (20 mL) the organic layer was removed The aqueous layer was extracted with CH2Cl2 (3×20 mL) the combined organics were concentrated the residue was dissolved in 2 N HCl (50 mL) This acidic mixture was washed with CH2Cl2 (3×20 mL) The basic mixture was extracted with CH2Cl2 (3×20 mL) dried concentrated

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

Procedure: A mixture of 2.4 g of 1-(2-chloro-ethyl)-4-fluoro-benzene, 30 mL of DMF, and 2.5 g of potassium thioacetate was stirred under nitrogen for 24 h. The mixture was diluted with 200 mL of water and extracted with 3×50 mL of dichloromethane. The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. Drying under vacuum gave the product as an oil: extracted with 3×50 mL of dichloromethane The combined organic layers were dried over magnesium sulfate concentrated under reduced pressure Drying under vacuum

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

Procedure: A mixture of 2.4 g of 1-(2-chloro-ethyl)-4-fluoro-benzene, 30 mL of DMF, and 2.5 g of potassium thioacetate was stirred under nitrogen for 24 h. The mixture was diluted with 200 mL of water and extracted with 3×50 mL of dichloromethane. The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. Drying under vacuum gave the product as an oil: extracted with 3×50 mL of dichloromethane The combined organic layers were dried over magnesium sulfate concentrated under reduced pressure Drying under vacuum

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

Procedure: A mixture of 7 g of 2-(4-fluoro-phenyl)-ethanol, 25 mL of chlorobenzene, 42 mL of 37% HCl, and 0.9 g of Aliquat® 336 (tricaprylylmethyl ammonium chloride) was heated to reflux for 3 days, cooled and extracted into 3×100 mL of hexane. The combined extracts were dried over magnesium sulfate and concentrated under reduced pressure. The resulting oil was a crude product of 1-(2-chloro-ethyl)-4-fluoro-benzene: was heated to reflux for 3 days cooled extracted into 3×100 mL of hexane The combined extracts were dried over magnesium sulfate concentrated under reduced pressure

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Piperazinone (1.20 g, 12.1 mmol), 1-fluoro-4-(2-chloroethyl)benzene (2.45 g, 12.1 mmol) and i-Pr2NEt (3.25 g, 4.5 ml, 25 mmol) were combined in acetonitrile (25 mL) and heated to 85° C. for 2 h. The mixture was concentrated and partitioned between H2O (20 mL) and CH2Cl2 (20 mL), and the organic layer was removed. The aqueous layer was extracted with CH2Cl2 (3×20 mL), the combined organics were concentrated, and the residue was dissolved in 2 N HCl (50 mL). This acidic mixture was washed with CH2Cl2 (3×20 mL) and then made basic with 6 N NaOH. The basic mixture was extracted with CH2Cl2 (3×20 mL), and the extracts were combined, dried and concentrated to provide the title compound (1.30 g, 48%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.18-7.13 (m, 2H), 7.00-6.94 (m, 2H), 6.45 (s, 1H), 3.39-3.35 (m, 2H), 3.20 (s, 2H), 2.78-2.62 (m, 6H). The mixture was concentrated partitioned between H2O (20 mL) and CH2Cl2 (20 mL) the organic layer was removed The aqueous layer was extracted with CH2Cl2 (3×20 mL) the combined organics were concentrated the residue was dissolved in 2 N HCl (50 mL) This acidic mixture was washed with CH2Cl2 (3×20 mL) The basic mixture was extracted with CH2Cl2 (3×20 mL) dried concentrated

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

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Piperazinone (1.20 g, 12.1 mmol), 1-fluoro-4-(2-chloroethyl)benzene (2.45 g, 12.1 mmol) and i-Pr2NEt (3.25 g, 4.5 ml, 25 mmol) were combined in acetonitrile (25 mL) and heated to 85° C. for 2 h. The mixture was concentrated and partitioned between H2O (20 mL) and CH2Cl2 (20 mL), and the organic layer was removed. The aqueous layer was extracted with CH2Cl2 (3×20 mL), the combined organics were concentrated, and the residue was dissolved in 2 N HCl (50 mL). This acidic mixture was washed with CH2Cl2 (3×20 mL) and then made basic with 6 N NaOH. The basic mixture was extracted with CH2Cl2 (3×20 mL), and the extracts were combined, dried and concentrated to provide the title compound (1.30 g, 48%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.18-7.13 (m, 2H), 7.00-6.94 (m, 2H), 6.45 (s, 1H), 3.39-3.35 (m, 2H), 3.20 (s, 2H), 2.78-2.62 (m, 6H). The mixture was concentrated partitioned between H2O (20 mL) and CH2Cl2 (20 mL) the organic layer was removed The aqueous layer was extracted with CH2Cl2 (3×20 mL) the combined organics were concentrated the residue was dissolved in 2 N HCl (50 mL) This acidic mixture was washed with CH2Cl2 (3×20 mL) The basic mixture was extracted with CH2Cl2 (3×20 mL) dried concentrated