cyclopropanethiol

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

Procedure: 1.78 g (44.6 mmol) of sodium hydride (60%) was added in portions to a solution of 3.00 g (40.5 mmol) of cyclopropane thiol (preparation according to: E. Block et al., J. Am. Chem. Soc. 1992, 114, 3492) in 100 ml THF/100 ml diethyl ether and was stirred for 30 minutes at room temperature. Then 6.00 g (38.7 mmol) of 1-fluoro-4-nitrobenzene was added in portions. The mixture was stirred for 2 hours at 40° C. After it had cooled, the mixture was put in water and was extracted with benzene (3×). The combined organic phases were concentrated by evaporation and the residue was purified chromatographically (hexane/ethyl acetate 95:5). 4.6 g (23.6 mmol; yield: 61%) of the product was obtained. The mixture was stirred for 2 hours at 40° C After it had cooled was extracted with benzene (3×) The combined organic phases were concentrated by evaporation the residue was purified chromatographically (hexane/ethyl acetate 95:5) 4.6 g (23.6 mmol; yield: 61%) of the product was obtained

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

Procedure: To a suspension of NaH (60% in mineral oil, 2.40 g) in THF (100 mL) was added dropwise cyclopropanethiol (0.25 M in Et2O, 160 mL) at 0° C. After stirring for 30 min, 5-bromo-2-fluoropyridine (3.52 g) was added in portions at 0° C. and then warmed to r.t. slowly. The reaction mixture was stirred at r.t. overnight. The reaction mixture was quenched with water (30 mL) and extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine (50 mL) and dried over Na2SO4. After filtration and evaporation of the solvent, the crude product was obtained and used in next step without further purification. The reaction mixture was stirred at r.t. overnight The reaction mixture was quenched with water (30 mL) extracted with ethyl acetate (50 mL×3) The combined organic layers were washed with brine (50 mL) dried over Na2SO4 After filtration and evaporation of the solvent

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

Procedure: To a suspension of NaH (60% in mineral oil, 2.40 g) in THF (100 mL) was added dropwise cyclopropanethiol (0.25 M in Et2O, 160 mL) at 0° C. After stirring for 30 min, 5-bromo-2-fluoropyridine (3.52 g) was added in portions at 0° C. and then warmed to r.t. slowly. The reaction mixture was stirred at r.t. overnight. The reaction mixture was quenched with water (30 mL) and extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine (50 mL) and dried over Na2SO4. After filtration and evaporation of the solvent, the crude product was obtained and used in next step without further purification. The reaction mixture was stirred at r.t. overnight The reaction mixture was quenched with water (30 mL) extracted with ethyl acetate (50 mL×3) The combined organic layers were washed with brine (50 mL) dried over Na2SO4 After filtration and evaporation of the solvent

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

Procedure: A 4% strength solution of 3.00 g (40.5 mmol) of cyclopropanethiol (preparation according to: E. Block et al., J. Am. Chem. Soc. 1992, 114, 3492) in THF/diethyl ether (1:1) was admixed in portions with 1.78 g (44.6 mmol) of sodium hydride (60%) and stirred for 30 minutes at room temperature. The portionwise addition of 6.00 g (38.7 mmol) of 1-fluoro-4-nitrobenzene was then carried out. The mixture was stirred at 40° C. for 2 hours. After cooling, the mixture was added to water and extracted (3×) with benzene. The combined organic phases were concentrated by evaporation and the residue was purified chromatographically (hexane/ethyl acetate 95:5). This gave 4.6 g (23.6 mmol; yield: 61%) of the product. The mixture was stirred at 40° C. for 2 hours After cooling extracted (3×) with benzene The combined organic phases were concentrated by evaporation the residue was purified chromatographically (hexane/ethyl acetate 95:5)

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

Procedure: 1.78 g (44.6 mmol) of sodium hydride (60%) was added in portions to a solution of 3.00 g (40.5 mmol) of cyclopropane thiol (preparation according to: E. Block et al., J. Am. Chem. Soc. 1992, 114, 3492) in 100 ml THF/100 ml diethyl ether and was stirred for 30 minutes at room temperature. Then 6.00 g (38.7 mmol) of 1-fluoro-4-nitrobenzene was added in portions. The mixture was stirred for 2 hours at 40° C. After it had cooled, the mixture was put in water and was extracted with benzene (3×). The combined organic phases were concentrated by evaporation and the residue was purified chromatographically (hexane/ethyl acetate 95:5). 4.6 g (23.6 mmol; yield: 61%) of the product was obtained. The mixture was stirred for 2 hours at 40° C After it had cooled was extracted with benzene (3×) The combined organic phases were concentrated by evaporation the residue was purified chromatographically (hexane/ethyl acetate 95:5) 4.6 g (23.6 mmol; yield: 61%) of the product was obtained

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

Procedure: Cyclopropanethiol in THF/diethyl ether was admixed in portions with sodium hydride and stirred at room temperature. 1-Fluoro-4-nitrobenzene was then added in portions. The mixture was stirred for 2 hours at 40° C. After cooling, the mixture was added to water and extracted with benzene (3×). The combined organic phases were concentrated by evaporation and the residue was purified by chromatography (hexane/acetic ester 95:5). (Yield: 61%). The mixture was stirred for 2 hours at 40° C After cooling extracted with benzene (3×) The combined organic phases were concentrated by evaporation the residue was purified by chromatography (hexane/acetic ester 95:5)

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

Procedure: An ether solution of cyclopropyl mercaptan synthesized from cyclopropyl bromide (50.0 g, 413 mmol) in accordance with the process described in literature (J. Am. Chem. Soc., 114, 3492 (1992)) was added dropwise to a solution of 60% sodium hydride (5.4 g, 135 mmol) in dimethyl sulfoxide (100 ml) under cooling with ice, and the mixture was stirred at room temperature for 10 minutes. A solution of ethyl bromodifluoroacetate (27.4 g, 135 mmol) in dimethyl sulfoxide (200 ml) was added dropwise to this solution under cooling with ice, and the resultant mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was poured into ice water to conduct extraction with ether. The solvent was distilled out of the resultant extract under reduced pressure. The resultant residue was distilled under reduced pressure to obtain the intended product (12.3 g; yield: 46.0%) as a colorless oil. under cooling with ice under cooling with ice After completion of the reaction extraction with ether The solvent was distilled out of the resultant extract under reduced pressure The resultant residue was distilled under reduced pressure to obtain the intended product (12.3 g; yield: 46.0%) as a colorless oil

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Freshly prepared cyclopropyl thiol in THF/diethyl ether (J. Am. Chem. Soc. 1992, 114(9), 3497) was added to 2-fluoro-5-nitrobenzaldehyde (3.4 g, 20 mmol, 1.0 eq.) and K2CO3 (4.83 g, 35 mmol) in DMF (20 mL). The mixture was stirred at 45° C. for 1.0 h and at rt over night. It was diluted with EtOAc and washed with water. The aqueous was extracted with EtOAc and the combined organic layers were washed with brine and dried over Na2SO4. After evaporation of solvent, the crude was tritutated with EtOAc/hexanes (70/120). The solid was collected to give 76A (3.2 g). The filtrate was condensed and triturated again to give a second crop of 76A (0.5 g, total yield 85%). 1H NMR (400 MHz, CDCl3) δ ppm 0.74-0.83 (m, 2H) 1.20-1.28 (m, 2H) 2.13-2.19 (m, 1H) 7.95 (d, J=9.23 Hz, 1H) 8.33 (dd, J=8.79, 2.64 Hz, 1H) 8.62 (d, J=2.64 Hz, 1H) 10.15 (s, 1H). washed with water The aqueous was extracted with EtOAc the combined organic layers were washed with brine dried over Na2SO4 After evaporation of solvent The solid was collected

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

Procedure: To a suspension of NaH (60% in mineral oil, 2.40 g) in THF (100 mL) was added dropwise cyclopropanethiol (0.25 M in Et2O, 160 mL) at 0° C. After stirring for 30 min, 5-bromo-2-fluoropyridine (3.52 g) was added in portions at 0° C. and then warmed to r.t. slowly. The reaction mixture was stirred at r.t. overnight. The reaction mixture was quenched with water (30 mL) and extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine (50 mL) and dried over Na2SO4. After filtration and evaporation of the solvent, the crude product was obtained and used in next step without further purification. The reaction mixture was stirred at r.t. overnight The reaction mixture was quenched with water (30 mL) extracted with ethyl acetate (50 mL×3) The combined organic layers were washed with brine (50 mL) dried over Na2SO4 After filtration and evaporation of the solvent