6-fluoro-3,4-dihydro-2H-naphthalen-1-one

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 solution of 6-fluoro-3,4-dihydro-2H-naphthalen-1-one (5.51 g, 33.56 mmol), benzenethiol (4.07 g, 3.79 mL, 36.92 mmol) and K2CO3 (9.28 g, 67.12 mmol) in 50 mL of N-methylpyrrolidinone (NMP) was heated to 80° C. under argon and stirred at 80° C. for 2 hours. The reaction mixture was poured into 500 mL of water and diluted with 300 mL of EtOAc. The layers were separated and the aqueous layer was extracted twice with 250 mL of EtOAc. The combined organic layers were washed with water, saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel using hexanes/EtOAc (9:1). Removal of solvent under reduced pressure provided 8.05 g (31.65 mmol, 94.31%) of 6-phenylsulfanyl-3,4-dihydro-2H-naphthalen-1-one as a pale yellow oil. MS: 255 (M+H)+. The layers were separated the aqueous layer was extracted twice with 250 mL of EtOAc The combined organic layers were washed with water, saturated brine dried over MgSO4 The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel Removal of solvent under reduced pressure

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

Procedure: A solution of 6-fluoro-3,4-dihydro-2H-naphthalen-1-one (5.51 g, 33.56 mmol), benzenethiol (4.07 g, 3.79 mL, 36.92 mmol) and K2CO3 (9.28 g, 67.12 mmol) in 50 mL of N-methyl pyrrolidinone (NMP) was heated to 80° C. under argon and stirred at 80° C. for 2 hours. The reaction mixture was poured into 500 mL of water and diluted with 300 mL of EtOAc. The layers were separated and the aqueous layer was extracted twice with 250 mL of EtOAc. The combined organic layers were washed with water, saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel using hexanes/EtOAc (9:1). Removal of solvent under reduced pressure provided 8.05 g (31.65 mmol, 94.31%) of 6-phenylsulfanyl-3,4-dihydro-2H-naphthalen-1-one as a pale yellow oil. MS: 255 (M+H)+. The layers were separated the aqueous layer was extracted twice with 250 mL of EtOAc The combined organic layers were washed with water, saturated brine dried over MgSO4 The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel Removal of solvent under reduced pressure

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

Procedure: Hexane washed sodium hydride (3.5 g of 60%, 88 mmole) was covered with 75 ml of tetrahydrofuran and 5.4 ml (64 mmole) of dimethylcarbonate was added in one portion. The solution was heated to reflux and 6-fluoro-3,4-dihydro-1(2H)-naphthlenone (7.2 g, 44 mmole) in 25 ml of tetrahydrofuran was added dropwise while maintaining reflux. After the addition was complete, the reaction was refluxed for 1.5 hours. The reaction was then cooled in an ice bath and 10% aqueous HCl solution was carefully added. The solution was diluted with ether and the aqueous phase was separated and extracted twice with ether. The combined organic phases were dried (MgSO4) and concentrated. The crude product was a pale yellow solid (9.6 g, 98% yield). was added in one portion The solution was heated to reflux while maintaining reflux After the addition the reaction was refluxed for 1.5 hours The reaction was then cooled in an ice bath the aqueous phase was separated extracted twice with ether The combined organic phases were dried (MgSO4) concentrated

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium azide 1.1 g (16.92 mmol) was added to a mixture of 6.0 mL of chloroform and 1.1 mL of water at 0° C. Concentrated sulfuric acid (0.44 mL) was added dropwise and the mixture stirred at 0° C. for two hours then filtered. The chloroform layer containing hydrazoic acid was added to a solution of 1.3 g (7.92 mmol) of 6-fluoro-1-tetralone (prepared by the method of Allinger and Jones, J. Org. Chem., 27, 70-76 (1962)) in 4.8 mL of chloroform. Additional sulfuric acid (2.16 mL) was added dropwise with stirring while maintaining the temperature below 40° C. The mixture was stirred at 40° C. for two hours then at room temperature for 16 hours. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was added to ice; the resulting recipitate was extracted with methylene chloride (5x). The combined extracts were washed with brine, dried over magnesium sulfate and filtered through a silica plug. Solvents were removed under vacuum to afford 162 mg (0.92 mmol, 11%) of the product. 1H NMR (300MHz, CDCl3): 2.21 (m,2H), 2.32 (t,7Hz,2H), 2.7 (t,7Hz,2H), 6.93 (m,3H), 7.8 (br s,1H). FAB-MS: calculated for C10H10FNO 179; found 180 (M+H,100%). then filtered The chloroform layer containing hydrazoic acid prepared by the method of Allinger and Jones, J with stirring while maintaining the temperature below 40° C The mixture was stirred at 40° C. for two hours at room temperature for 16 hours The mixture was transferred to a separatory funnel the layers were separated The aqueous layer was added to ice the resulting recipitate was extracted with methylene chloride (5x) The combined extracts were washed with brine dried over magnesium sulfate filtered through a silica plug Solvents were removed under vacuum

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

Procedure: A solution of 6-fluoro-3,4-dihydro-2H-naphthalen-1-one (5.51 g, 33.56 mmol), benzenethiol (4.07 g, 3.79 mL, 36.92 mmol) and K2CO3 (9.28 g, 67.12 mmol) in 50 mL of N-methyl pyrrolidinone (NMP) was heated to 80° C. under argon and stirred at 80° C. for 2 hours. The reaction mixture was poured int 500 mL of water and diluted with 300 mL of EtOAc. The layers were separated and the aqueous layer was extracted twice with 250 mL of EtOAc. The combined organic layers were washed with water, saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel using hexanes/EtOAc (9:1). Removal of solvent under reduced pressure provided 8.05 g (31.65 mmol, 94.31%) of 6-phenylsulfanyl-3,4-dihydro-2H-naphthalen-1-one as a pale yellow oil. MS: 255 (M+H)+. The layers were separated the aqueous layer was extracted twice with 250 mL of EtOAc The combined organic layers were washed with water, saturated brine dried over MgSO4 The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel Removal of solvent under reduced pressure

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

Procedure: A solution of 6-fluoro-3,4-dihydro-2H-naphthalen-1-one (5.51 g, 33.56 mmol), benzenethiol (4.07 g, 3.79 mL, 36.92 mmol) and K2CO3 (9.28 g, 67.12 mmol) in 50 mL of N-methyl pyrrolidinone (NMP) was heated to 80° C. under argon and stirred at 80° C. for 2 hours. The reaction mixture was poured int 500 mL of water and diluted with 300 mL of EtOAc. The layers were separated and the aqueous layer was extracted twice with 250 mL of EtOAc. The combined organic layers were washed with water, saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel using hexanes/EtOAc (9:1). Removal of solvent under reduced pressure provided 8.05 g (31.65 mmol, 94.31%) of 6-phenylsulfanyl-3,4-dihydro-2H-naphthalen-1-one as a pale yellow oil. MS: 255 (M+H)+. The layers were separated the aqueous layer was extracted twice with 250 mL of EtOAc The combined organic layers were washed with water, saturated brine dried over MgSO4 The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel Removal of solvent under reduced pressure

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

Procedure: Over a solution of 6-fluorotetralone (6-fluoro-3,4-dihydro-1 H-naphthalen-2-one; 1 equivalent) and ammonium acetate (5 equivalents) in a 2:1 mixture of MeOH:THF (0.24 M), was carefully added NaCNBH3 (2 eq), and the reaction mixture was stirred at room temperature for 2 hours. Concentrated HCl was added at 0° C. until the pH was less than 2, and the MeOH was removed in vacuo. The residue was taken up in water and extracted with CHCl3 (2×). The aqueous solution was basified with solid KOH and extracted with CHCl3 (3×). The combined extracts were dried (MgSO4) and evaporated in vacuo to give the titled compound. the MeOH was removed in vacuo extracted with CHCl3 (2×) extracted with CHCl3 (3×) The combined extracts were dried (MgSO4) evaporated in vacuo

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

Procedure: A solution of 6-fluoro-3,4-dihydro-2H-naphthalen-1-one (5.51 g, 33.56 mmol), benzenethiol (4.07 g, 3.79 mL, 36.92 mmol) and K2CO3 (9.28 g, 67.12 mmol) in 50 mL of N-methylpyrrolidinone (NMP) was heated to 80° C. under argon and stirred at 80° C. for 2 hours. The reaction mixture was poured int 500 mL of water and diluted with 300 mL of EtOAc. The layers were separated and the aqueous layer was extracted twice with 250 mL of EtOAc. The combinded organic layers were washed with water, saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel using hexanes/EtOAc (9:1). Removal of solvent under reduced pressure provided 8.05 g (31.65 mmol, 94.31%) of 6-phenylsulfanyl-3,4-dihydro-2H-naphthalen-1-one as a pale yellow oil. MS: 255 (M+H)+. The layers were separated the aqueous layer was extracted twice with 250 mL of EtOAc The combinded organic layers were washed with water, saturated brine dried over MgSO4 The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel Removal of solvent under reduced pressure

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

Procedure: A solution of 6-fluoro-3,4-dihydro-2H-naphthalen-1-one (5.51 g, 33.56 mmol), benzenethiol (4.07 g, 3.79 mL, 36.92 mmol) and K2CO3 (9.28 g, 67.12 mmol) in 50 mL of N-methylpyrrolidinone (NMP) was heated to 80° C. under argon and stirred at 80° C. for 2 hours. The reaction mixture was poured int 500 mL of water and diluted with 300 mL of EtOAc. The layers were separated and the aqueous layer was extracted twice with 250 mL of EtOAc. The combinded organic layers were washed with water, saturated brine, and then dried over MgSO4. The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel using hexanes/EtOAc (9:1). Removal of solvent under reduced pressure provided 8.05 g (31.65 mmol, 94.31%) of 6-phenylsulfanyl-3,4-dihydro-2H-naphthalen-1-one as a pale yellow oil. MS: 255 (M+H)+. The layers were separated the aqueous layer was extracted twice with 250 mL of EtOAc The combinded organic layers were washed with water, saturated brine dried over MgSO4 The solvent was removed under reduced pressure to yield an oil which was eluted through silica gel Removal of solvent under reduced pressure