7-bromo-2-tert-butyl-3,4-dihydro-2H-naphthalen-1-one

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step b—To a solution of 109 (3 g, 10.7 mmol) and HOAc (40 mL) stirred at RT under N2 was added dropwise via cannula a solution of bromine (1.88 g, 605 μL, 11.7 mmol) in HOAc (20.0 mL) over 20 min. The solution was stirred for 1 h at RT then warmed reaction to 50° C. and stirred 1 h. An aliquot of neat bromine (100 μL) was added and heating continued. The total heating time was 2.5 h. The reaction mixture was poured over ice, partitioned between EtOAc and H2O and aqueous phase was neutralized with satd. aq. NaHCO3. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The product was purified by SiO2 chromatography eluting with hexanes to afford 3.8 g (quantitative) of 110. then warmed reaction to 50° C. stirred 1 h heating The total heating time was 2.5 h The reaction mixture was poured over ice partitioned between EtOAc and H2O and aqueous phase The organic layer was separated washed with brine dried (MgSO4) filtered concentrated The product was purified by SiO2 chromatography eluting with hexanes

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—A solution of (7-bromo-3,4-dihydronaphthalen-1-yloxy)trimethylsilane (6.85 g, 11.5 mmol, CASRN 309929-09-7) and DCM (23.0 mL) was cooled to −40° C. 2-Chloro-2-methylpropane (1.12 g, 1.32 mL, 12.1 mmol) was added and the solution stirred under nitrogen. A solution of TiCl4 (2.19 g, 1.27 mL, 11.5 mmol) in DCM (6 mL) was added dropwise while maintaining the solution at −40° C. Soon after addition was complete TLC indicated ca. 50% conversion. The reaction was stirred at RT over the weekend then poured onto ice. The mixture was partitioned between EtOAc and H2O and aqueous layer was neutralized with satd. aq. NaHCO3. The mixture was filtered through a plug of celite to a remove chunky white precipitate. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The crude product was applied to a hexane equilibrated SiO2 column and eluted with an EtOAc/hexane gradient (0 to 5% EtOAc) to afford 3.26 g (quantitative) of 7-bromo-2-tert-butyl-3,4-dihydro-2H-naphthalen-1-one (109) a yellow solid. Soon after addition The reaction was stirred at RT over the weekend then poured onto ice The mixture was partitioned between EtOAc and H2O and aqueous layer The mixture was filtered through a plug of celite to a remove chunky white precipitate The organic layer was separated washed with brine dried (MgSO4) filtered concentrated eluted with an EtOAc/hexane gradient (0 to 5% EtOAc)

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—A solution of (7-bromo-3,4-dihydronaphthalen-1-yloxy)trimethylsilane (6.85 g, 11.5 mmol, CASRN 309929-09-7) and DCM (23.0 mL) was cooled to −40° C. 2-Chloro-2-methylpropane (1.12 g, 1.32 mL, 12.1 mmol) was added and the solution stirred under nitrogen. A solution of TiCl4 (2.19 g, 1.27 mL, 11.5 mmol) in DCM (6 mL) was added dropwise while maintaining the solution at −40° C. Soon after addition was complete TLC indicated ca. 50% conversion. The reaction was stirred at RT over the weekend then poured onto ice. The mixture was partitioned between EtOAc and H2O and aqueous layer was neutralized with satd. aq. NaHCO3. The mixture was filtered through a plug of celite to a remove chunky white precipitate. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The crude product was applied to a hexane equilibrated SiO2 column and eluted with an EtOAc/hexane gradient (0 to 5% EtOAc) to afford 3.26 g (quantitative) of 7-bromo-2-tert-butyl-3,4-dihydro-2H-naphthalen-1-one (109) a yellow solid. Soon after addition The reaction was stirred at RT over the weekend then poured onto ice The mixture was partitioned between EtOAc and H2O and aqueous layer The mixture was filtered through a plug of celite to a remove chunky white precipitate The organic layer was separated washed with brine dried (MgSO4) filtered concentrated eluted with an EtOAc/hexane gradient (0 to 5% EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step b—To a solution of 109 (3 g, 10.7 mmol) and HOAc (40 mL) stirred at RT under N2 was added dropwise via cannula a solution of bromine (1.88 g, 605 μL, 11.7 mmol) in HOAc (20.0 mL) over 20 min. The solution was stirred for 1 h at RT then warmed reaction to 50° C. and stirred 1 h. An aliquot of neat bromine (100 μL) was added and heating continued. The total heating time was 2.5 h. The reaction mixture was poured over ice, partitioned between EtOAc and H2O and aqueous phase was neutralized with satd. aq. NaHCO3. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The product was purified by SiO2 chromatography eluting with hexanes to afford 3.8 g (quantitative) of 110. then warmed reaction to 50° C. stirred 1 h heating The total heating time was 2.5 h The reaction mixture was poured over ice partitioned between EtOAc and H2O and aqueous phase The organic layer was separated washed with brine dried (MgSO4) filtered concentrated The product was purified by SiO2 chromatography eluting with hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step b—To a solution of 109 (3 g, 10.7 mmol) and HOAc (40 mL) stirred at RT under N2 was added dropwise via cannula a solution of bromine (1.88 g, 605 μL, 11.7 mmol) in HOAc (20.0 mL) over 20 min. The solution was stirred for 1 h at RT then warmed reaction to 50° C. and stirred 1 h. An aliquot of neat bromine (100 μL) was added and heating continued. The total heating time was 2.5 h. The reaction mixture was poured over ice, partitioned between EtOAc and H2O and aqueous phase was neutralized with satd. aq. NaHCO3. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The product was purified by SiO2 chromatography eluting with hexanes to afford 3.8 g (quantitative) of 110. then warmed reaction to 50° C. stirred 1 h heating The total heating time was 2.5 h The reaction mixture was poured over ice partitioned between EtOAc and H2O and aqueous phase The organic layer was separated washed with brine dried (MgSO4) filtered concentrated The product was purified by SiO2 chromatography eluting with hexanes

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—A solution of (7-bromo-3,4-dihydronaphthalen-1-yloxy)trimethylsilane (6.85 g, 11.5 mmol, CASRN 309929-09-7) and DCM (23.0 mL) was cooled to −40° C. 2-Chloro-2-methylpropane (1.12 g, 1.32 mL, 12.1 mmol) was added and the solution stirred under nitrogen. A solution of TiCl4 (2.19 g, 1.27 mL, 11.5 mmol) in DCM (6 mL) was added dropwise while maintaining the solution at −40° C. Soon after addition was complete TLC indicated ca. 50% conversion. The reaction was stirred at RT over the weekend then poured onto ice. The mixture was partitioned between EtOAc and H2O and aqueous layer was neutralized with satd. aq. NaHCO3. The mixture was filtered through a plug of celite to a remove chunky white precipitate. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The crude product was applied to a hexane equilibrated SiO2 column and eluted with an EtOAc/hexane gradient (0 to 5% EtOAc) to afford 3.26 g (quantitative) of 7-bromo-2-tert-butyl-3,4-dihydro-2H-naphthalen-1-one (109) a yellow solid. Soon after addition The reaction was stirred at RT over the weekend then poured onto ice The mixture was partitioned between EtOAc and H2O and aqueous layer The mixture was filtered through a plug of celite to a remove chunky white precipitate The organic layer was separated washed with brine dried (MgSO4) filtered concentrated eluted with an EtOAc/hexane gradient (0 to 5% EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step b—To a solution of 109 (3 g, 10.7 mmol) and HOAc (40 mL) stirred at RT under N2 was added dropwise via cannula a solution of bromine (1.88 g, 605 μL, 11.7 mmol) in HOAc (20.0 mL) over 20 min. The solution was stirred for 1 h at RT then warmed reaction to 50° C. and stirred 1 h. An aliquot of neat bromine (100 μL) was added and heating continued. The total heating time was 2.5 h. The reaction mixture was poured over ice, partitioned between EtOAc and H2O and aqueous phase was neutralized with satd. aq. NaHCO3. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The product was purified by SiO2 chromatography eluting with hexanes to afford 3.8 g (quantitative) of 110. then warmed reaction to 50° C. stirred 1 h heating The total heating time was 2.5 h The reaction mixture was poured over ice partitioned between EtOAc and H2O and aqueous phase The organic layer was separated washed with brine dried (MgSO4) filtered concentrated The product was purified by SiO2 chromatography eluting with hexanes

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—A solution of (7-bromo-3,4-dihydronaphthalen-1-yloxy)trimethylsilane (6.85 g, 11.5 mmol, CASRN 309929-09-7) and DCM (23.0 mL) was cooled to −40° C. 2-Chloro-2-methylpropane (1.12 g, 1.32 mL, 12.1 mmol) was added and the solution stirred under nitrogen. A solution of TiCl4 (2.19 g, 1.27 mL, 11.5 mmol) in DCM (6 mL) was added dropwise while maintaining the solution at −40° C. Soon after addition was complete TLC indicated ca. 50% conversion. The reaction was stirred at RT over the weekend then poured onto ice. The mixture was partitioned between EtOAc and H2O and aqueous layer was neutralized with satd. aq. NaHCO3. The mixture was filtered through a plug of celite to a remove chunky white precipitate. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The crude product was applied to a hexane equilibrated SiO2 column and eluted with an EtOAc/hexane gradient (0 to 5% EtOAc) to afford 3.26 g (quantitative) of 7-bromo-2-tert-butyl-3,4-dihydro-2H-naphthalen-1-one (109) a yellow solid. Soon after addition The reaction was stirred at RT over the weekend then poured onto ice The mixture was partitioned between EtOAc and H2O and aqueous layer The mixture was filtered through a plug of celite to a remove chunky white precipitate The organic layer was separated washed with brine dried (MgSO4) filtered concentrated eluted with an EtOAc/hexane gradient (0 to 5% EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step b—To a solution of 109 (3 g, 10.7 mmol) and HOAc (40 mL) stirred at RT under N2 was added dropwise via cannula a solution of bromine (1.88 g, 605 μL, 11.7 mmol) in HOAc (20.0 mL) over 20 min. The solution was stirred for 1 h at RT then warmed reaction to 50° C. and stirred 1 h. An aliquot of neat bromine (100 μL) was added and heating continued. The total heating time was 2.5 h. The reaction mixture was poured over ice, partitioned between EtOAc and H2O and aqueous phase was neutralized with satd. aq. NaHCO3. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The product was purified by SiO2 chromatography eluting with hexanes to afford 3.8 g (quantitative) of 110. then warmed reaction to 50° C. stirred 1 h heating The total heating time was 2.5 h The reaction mixture was poured over ice partitioned between EtOAc and H2O and aqueous phase The organic layer was separated washed with brine dried (MgSO4) filtered concentrated The product was purified by SiO2 chromatography eluting with hexanes

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: step a—A solution of (7-bromo-3,4-dihydronaphthalen-1-yloxy)trimethylsilane (6.85 g, 11.5 mmol, CASRN 309929-09-7) and DCM (23.0 mL) was cooled to −40° C. 2-Chloro-2-methylpropane (1.12 g, 1.32 mL, 12.1 mmol) was added and the solution stirred under nitrogen. A solution of TiCl4 (2.19 g, 1.27 mL, 11.5 mmol) in DCM (6 mL) was added dropwise while maintaining the solution at −40° C. Soon after addition was complete TLC indicated ca. 50% conversion. The reaction was stirred at RT over the weekend then poured onto ice. The mixture was partitioned between EtOAc and H2O and aqueous layer was neutralized with satd. aq. NaHCO3. The mixture was filtered through a plug of celite to a remove chunky white precipitate. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. The crude product was applied to a hexane equilibrated SiO2 column and eluted with an EtOAc/hexane gradient (0 to 5% EtOAc) to afford 3.26 g (quantitative) of 7-bromo-2-tert-butyl-3,4-dihydro-2H-naphthalen-1-one (109) a yellow solid. Soon after addition The reaction was stirred at RT over the weekend then poured onto ice The mixture was partitioned between EtOAc and H2O and aqueous layer The mixture was filtered through a plug of celite to a remove chunky white precipitate The organic layer was separated washed with brine dried (MgSO4) filtered concentrated eluted with an EtOAc/hexane gradient (0 to 5% EtOAc)