1-ethyl-4-fluorobenzene

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-ethyl-4-fluorobenzene (0.248 g, 2 mmol), NBS (0.35 g, 2 mmol) and benzoyl peroxide (0.14 g, 0.6 mmol) were dissolved in 20 mL CCl4. The mixture was stirred at 80° C. for 5 hours and then the reaction was conc. in vacuo and resulting oil was purified via silica gel chromatography (PE-EtOAC 5:1) to give the title compound (330 mg, 80%) as a yellow oil. LCMS 202 (M+H+). resulting oil was purified via silica gel chromatography (PE-EtOAC 5:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-ethyl-4-fluorobenzene (0.248 g, 2 mmol), NBS (0.35 g, 2 mmol) and benzoyl peroxide (0.14 g, 0.6 mmol) were dissolved in 20 mL CCl4. The mixture was stirred at 80° C. for 5 hours and then the reaction was conc. in vacuo and resulting oil was purified via silica gel chromatography (PE-EtOAC 5:1) to give the title compound (330 mg, 80%) as a yellow oil. LCMS 202 (M+H+). resulting oil was purified via silica gel chromatography (PE-EtOAC 5:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-ethyl-4-fluorobenzene (0.248 g, 2 mmol), NBS (0.35 g, 2 mmol) and benzoyl peroxide (0.14 g, 0.6 mmol) were dissolved in 20 mL CCl4. The mixture was stirred at 80° C. for 5 hours and then the reaction was conc. in vacuo and resulting oil was purified via silica gel chromatography (PE-EtOAC 5:1) to give the title compound (330 mg, 80%) as a yellow oil. LCMS 202 (M+H+). resulting oil was purified via silica gel chromatography (PE-EtOAC 5:1)

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-ethyl-4-fluorobenzene (10 g, 80.6 mmol) and PMDTA (17 mL) in THF (60 mL) cooled to −78° C. was added 1.6 M n-butyl lithium (56 mL, 89 mmol) dropwise and the mixture stirred for 40 min at −60° C. Mixture cooled to −78° C. and added DMF (16 mL, 202 mmol) before allowing the mixture to warm to 23° C. Quenched with aqueous NH4Cl and extracted with EtOAc (3×50 mL). Organic layer was washed with H2O and brine before concentrating to afford 11.6 g of Intermediate 311.2. 1H-NMR (CDCl3)=1.18 (t, 3 H), δ 2.58 (q, 2 H), δ 7.04 (t, 1 H), δ 7.35 (m, 1 H), δ 7.62 (m, 1 H), δ 10.31 (s, 1 H). Mixture cooled to −78° C. to warm to 23° C Quenched with aqueous NH4Cl extracted with EtOAc (3×50 mL) Organic layer was washed with H2O and brine before concentrating

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-ethyl-4-fluorobenzene (5.0 g, 40.3 mmol) and PMDTA (8.5 mL, 40.7 mmol) in 20 mL THF at −40° C., was added BuLi (1.4 M in hexanes, 31.6 mL, 44.3 mmol). The tan suspension was stirred at −60° C. for 40 min, was recooled to −78° C., then B(OMe)3 (9.03 mL, 80.6 mmol). The mixture was stirred at −78° C. for 30 min, then was allowed to warm to rt. The reaction was quenched with 8 mL AcOH, then was cooled to 0° C. and treated with 9.8 mL 30% H2O2. The mixture was stirred for 30 min, then was quenched with aq. Na2SO3. The mixture was diluted with hexanes, washed with H2O (3×) and brine, dried (Na2SO4), filtered through 2″ silica gel (eluting with 20% EtOAc/hexanes), then concentrated to afford 5.42 g of Intermediate 188.1 as a pale yellow oil. was recooled to −78° C. The mixture was stirred at −78° C. for 30 min to warm to rt The reaction was quenched with 8 mL AcOH was cooled to 0° C. treated with 9.8 mL 30% H2O2 The mixture was stirred for 30 min was quenched with aq. Na2SO3 The mixture was diluted with hexanes washed with H2O (3×) and brine dried (Na2SO4) filtered through 2″ silica gel (eluting with 20% EtOAc/hexanes) concentrated

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

Procedure: A solution of 15.5 g of 4-ethylfluorobenzene and 14.6 g of N,N,N′N′-tetramethylethylenediamine in 500 ml of THF was cooled to −75° C. under a nitrogen atmosphere, and then 126 ml of s-butyllithium (0.99M, cyclohexane solution) was added and the mixture was stirred for 2 hours. After then adding 28 ml of trimethyl borate, the reaction mixture was warmed to room temperature and 14.4 ml of acetic acid was added. After stirring for 30 minutes, the reaction mixture was cooled to 0° C., and then 28.4 ml of 30% aqueous hydrogen peroxide was added and the mixture was stirred at room temperature for 18 hours. Next, 500 ml of saturated aqueous sodium sulfite was added to the reaction mixture and extraction was performed with 1 liter of diethyl ether. The organic layer was washed with 500 ml of water and 500 ml of saturated aqueous sodium chloride in that order and dried over anhydrous magnesium sulfate, the desiccating agent was filtered, and the filtrate was concentrated under reduced pressure. The residue was subjected to distillation to give the title compound (16.35 g) as a colorless liquid (boiling point: 76-80° C., 17 mmHg). After stirring for 30 minutes the reaction mixture was cooled to 0° C. the mixture was stirred at room temperature for 18 hours The organic layer was washed with 500 ml of water and 500 ml of saturated aqueous sodium chloride in that order dried over anhydrous magnesium sulfate the desiccating agent was filtered the filtrate was concentrated under reduced pressure The residue was subjected to distillation

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

Procedure: A solution of 15.5 g of 4-ethylfluorobenzene and 14.6 g of N,N,N′N′-tetramethylethylenediamine in 500 ml of THF was cooled to −75° C. under a nitrogen atmosphere, and then 126 ml of s-butyllithium (0.99M, cyclohexane solution) was added and the mixture was stirred for 2 hours. After then adding 28 ml of trimethyl borate, the reaction mixture was warmed to room temperature and 14.4 ml of acetic acid was added. After stirring for 30 minutes, the reaction mixture was cooled to 0° C., and then 28.4 ml of 30% aqueous hydrogen peroxide was added and the mixture was stirred at room temperature for 18 hours. Next, 500 ml of saturated aqueous sodium sulfite was added to the reaction mixture and extraction was performed with 1 liter of diethyl ether. The organic layer was washed with 500 ml of water and 500 ml of saturated aqueous sodium chloride in that order and dried over anhydrous magnesium sulfate, the desiccating agent was filtered, and the filtrate was concentrated under reduced pressure. The residue was subjected to distillation to give the title compound (16.35 g) as a colorless liquid (boiling point: 76-80° C., 17 mmHg). After stirring for 30 minutes the reaction mixture was cooled to 0° C. the mixture was stirred at room temperature for 18 hours The organic layer was washed with 500 ml of water and 500 ml of saturated aqueous sodium chloride in that order dried over anhydrous magnesium sulfate the desiccating agent was filtered the filtrate was concentrated under reduced pressure The residue was subjected to distillation

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-ethyl-4-fluorobenzene (0.248 g, 2 mmol), NBS (0.35 g, 2 mmol) and benzoyl peroxide (0.14 g, 0.6 mmol) were dissolved in 20 mL CCl4, The mixture was stirred at 80° C. for 5 hours and then the reaction was conc. in vacuo and resulting oil was purified via silica gel chromatography (PE-EtOAC 5:1) to give the title compound (330 mg, 80%) as a yellow oil. LCMS 202 (M+H+). resulting oil was purified via silica gel chromatography (PE-EtOAC 5:1)

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

Procedure: To a solution of 1-ethyl-4-fluorobenzene (7.2 g, 58 mmol) in THF (30 mL) and N,N,N′,N″,N″-pentamethyldiethylenetriamine (3.0 mL) was added n-BuLi (1.6M in hexane, 42 mL) at −78° C. After 1 h stirring, trimethyl borate (13 mL) was added. The mixture was stirred from −78° C. to rt overnight. It was quenched by acetic acid (5.0 mL) and hydrogen peroxide solution (30% in water) at 0° C. The mixture was stirred for 2 h before extracted with EtOAc. The organic extracts were washed with brine, dried over MgSO4 and concentrate to give 118A (7.6 g, 94% yield) as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.19 (t, J=7.69 Hz, 3H) 2.56 (q, J=7.62 Hz, 2H) 6.60-6.71 (m, 1H) 6.83 (dd, J=8.79, 2.20 Hz, 1H) 6.95 (dd, J=10.55, 8.35 Hz, 1H). The mixture was stirred from −78° C. to rt overnight It was quenched by acetic acid (5.0 mL) and hydrogen peroxide solution (30% in water) at 0° C The mixture was stirred for 2 h before extracted with EtOAc The organic extracts were washed with brine dried over MgSO4 concentrate

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

Procedure: A solution of 15.5 g of 4-ethylfluorobenzene and 14.6 g of N,N,N′N′-tetramethylethylenediamine in 500 ml of THF was cooled to −75° C. under a nitrogen atmosphere, and then 126 ml of s-butyllithium (0.99M, cyclohexane solution) was added and the mixture was stirred for 2 hours. After then adding 28 ml of trimethyl borate, the reaction mixture was warmed to room temperature and 14.4 ml of acetic acid was added. After stirring for 30 minutes, the reaction mixture was cooled to 0° C., and then 28.4 ml of 30% aqueous hydrogen peroxide was added and the mixture was stirred at room temperature for 18 hours. Next, 500 ml of saturated aqueous sodium sulfite was added to the reaction mixture and extraction was performed with 1 liter of diethyl ether. The organic layer was washed with 500 ml of water and 500 ml of saturated aqueous sodium chloride in that order and dried over anhydrous magnesium sulfate, the desiccating agent was filtered, and the filtrate was concentrated under reduced pressure. The residue was subjected to distillation to give the title compound (16.35 g) as a colorless liquid (boiling point: 76-80° C., 17 mmHg). After stirring for 30 minutes the reaction mixture was cooled to 0° C. the mixture was stirred at room temperature for 18 hours The organic layer was washed with 500 ml of water and 500 ml of saturated aqueous sodium chloride in that order dried over anhydrous magnesium sulfate the desiccating agent was filtered the filtrate was concentrated under reduced pressure The residue was subjected to distillation