2-benzyl-4-bromophenol

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

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

Procedure: 9.48 ml (152 mmol, 10 eqv) iodomethane was added to a suspension of 4.00 g (15.2 mmol) 2-Benzyl-4-bromo-phenol (20) and 10.50 g (76 mmol, 5 eqv) K2CO3 in 70 ml acetone and the resulting mixture was refluxed for 24 h. After adding water and aq. NH3-solution, the aq. layer was extracted with Et2O. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2) yielded 4.11 g (14.8 mmol, 98%) 21 as a colorless liquid: Rf (CH2Cl2) 0.77; 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.92 (s, 2H), 6.72 (d, 1H, J=8.59 Hz), 7.18 (m, 4H), 7.27 (m, 3H); LRMS (EI) m/z 279 (17), 278 (95), 277 (18), 276 (96), 263 (14), 261 (17), 198 (18), 197 (65), 182 (34), 181 (31), 166 (20), 165 (56), 154 (19), 153 (24), 152 (29), 92 (11), 91 (100), 77 (13), 76 (16), 63 (13); HRMS (EI) Calcd. for C14H13BrO: 276.014976. Found: 276.014234. the resulting mixture was refluxed for 24 h the aq. layer was extracted with Et2O fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: A solution of 13.24 g (99.3 mmol, 4.1 eqv) AlCl3 in 85 ml dry Et2O was added cautiously under stirring to a suspension of 3.91 g (102.9 mmol, 4.2 eqv) LiAlH4 in 100 ml dry Et2O. After complete addition the resulting mixture was stirred for 30 min at rt and then a solution of 6.85 g (24.5 mmol) 4-Bromo-2-(hydroxy-phenyl-methyl)-phenol (19) in 80 ml dry Et2O was added dropwise. The mixture was refluxed for 12 h and after that cooled to 0° C. After adding cautiously 60 ml of a mixture of Et2O/MeOH (1:1), 170 ml 1 N HCl-solution was added and the mixture was extracted with Et2O. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2) yielded 4.00 g (15.2 mmol, 62%) 20 as a colorless liquid: Rf (CH2Cl2) 0.41; 1H NMR (500 MHz, CDCl3) δ 3.95 (s, 2H), 4.64 (s, 1H), 6.67 (dd, 1H, J1=8.04 Hz, J2=0.79 Hz), 7.23 (m, 5H), 7.31 (m, 2H); LRMS (EI) m/z 265 (17), 264 (98), 263 (21), 262 (100), 186 (53), 184 (49), 183 (78), 182 (18), 181 (27), 165 (49), 153 (23), 152 (26), 91 (29), 84 (14), 78 (25), 77 (31), 76 (16), 63 (15); HRMS (EI) Calcd. for C13H11BrO: 261.999326. Found: 261.998568. After complete addition the resulting mixture The mixture was refluxed for 12 h after that cooled to 0° C was added the mixture was extracted with Et2O fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: 452 mg (1.35 mmol) 4-(2-Cyanoethyl)-2-isobutylphenyl-trifluormethanesulfonate (6), 637.8 mg (1.70 mmol, 1.26 eq.) 2-(4-Methoxy-3-naphthalen-1-ylmethyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (64) and 236.8 mg (205 μmol, 0.15 eq.) Pd(Ph3P)4 were dissolved in 20 ml DME/EtOH (9+1). To this yellow solution 1.35 ml (2.70 mmol, 2 eq.) of a 2 M aq. Na2CO3-solution was added and the resulting mixture was heated at 80° C. for 15 h. After concentrating the mixture in vacuo the residue was taken up in water and extracted with CH2Cl2. The comb. org. fractions were dried over MgSO4 and evaporated. Column chromatography (hexanes/EtOAc (3+1)) yielded 513.8 mg (1.19 mmol, 87.78%) 3-(2-Isobutyl-4′-methoxy-3′-naphthalen-1-ylm Rf (hexanes/EtOAc (3+1))=0.40. 1H-NMR (500 MHz, CDCl3): δ=0.51 (d, 6H, J=6.62 Hz, 2*CH3), 1.42 (m, 1H, CH), 2.17 (d, 2H, J=7.25 Hz, CH2), 2.56 (t, 2H, J=7.41 Hz, CH2CH2CN), 2.87 (t, 2H, J=7.41 Hz, CH2CH2CN), 3.91 (s, 3H, OCH3), 4.42 (s, 2H, CH2Naphthyl), 6.71 (d, 1H, J=2.21 Hz), 6.94 (m, 3H), 7.00 (d, 1H, J=7.72 Hz), 7.04 (dd, 1H, J1=8.36 Hz, J2=2.36 Hz), 7.22 (m, 1H), 7.35 (m, 1H), 7.41 (m, 2H), 7.69 (d, 1H, J=8.20 Hz), 7.81 (m, 1H), 7.97 (m, 1H). MS (EI): m/z=434 (16), 433 (48), 336 (9), 335 (56), 294 (11), 293 (83), 292 (17), 277 (9), 265 (20), 264 (100), 253 (29). HR-MS (EI): Calcd. for C31H31NO: 433.240564. Found: 433.241264.

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

Procedure: 9.48 ml (152 mmol, 10 eqv) iodomethane was added to a suspension of 4.00 g (15.2 mmol) 2-Benzyl-4-bromo-phenol (20) and 10.50 g (76 mmol, 5 eqv) K2CO3 in 70 ml acetone and the resulting mixture was refluxed for 24 h. After adding water and aq. NH3-solution, the aq. layer was extracted with Et2O. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2) yielded 4.11 g (14.8 mmol, 98%) 21 as a colorless liquid: Rf (CH2Cl2) 0.77; 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.92 (s, 2H), 6.72 (d, 1H, J=8.59 Hz), 7.18 (m, 4H), 7.27 (m, 3H); LRMS (EI) m/z 279 (17), 278 (95), 277 (18), 276 (96), 263 (14), 261 (17), 198 (18), 197 (65), 182 (34), 181 (31), 166 (20), 165 (56), 154 (19), 153 (24), 152 (29), 92 (11), 91 (100), 77 (13), 76 (16), 63 (13); HRMS (EI) Calcd. for C14H13BrO: 276.014976. Found: 276.014234. the resulting mixture was refluxed for 24 h the aq. layer was extracted with Et2O fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: A solution of 13.24 g (99.3 mmol, 4.1 eqv) AlCl3 in 85 ml dry Et2O was added cautiously under stirring to a suspension of 3.91 g (102.9 mmol, 4.2 eqv) LiAlH4 in 100 ml dry Et2O. After complete addition the resulting mixture was stirred for 30 min at rt and then a solution of 6.85 g (24.5 mmol) 4-Bromo-2-(hydroxy-phenyl-methyl)-phenol (19) in 80 ml dry Et2O was added dropwise. The mixture was refluxed for 12 h and after that cooled to 0° C. After adding cautiously 60 ml of a mixture of Et2O/MeOH (1:1), 170 ml 1 N HCl-solution was added and the mixture was extracted with Et2O. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2) yielded 4.00 g (15.2 mmol, 62%) 20 as a colorless liquid: Rf (CH2Cl2) 0.41; 1H NMR (500 MHz, CDCl3) δ 3.95 (s, 2H), 4.64 (s, 1H), 6.67 (dd, 1H, J1=8.04 Hz, J2=0.79 Hz), 7.23 (m, 5H), 7.31 (m, 2H); LRMS (EI) m/z 265 (17), 264 (98), 263 (21), 262 (100), 186 (53), 184 (49), 183 (78), 182 (18), 181 (27), 165 (49), 153 (23), 152 (26), 91 (29), 84 (14), 78 (25), 77 (31), 76 (16), 63 (15); HRMS (EI) Calcd. for C13H11BrO: 261.999326. Found: 261.998568. After complete addition the resulting mixture The mixture was refluxed for 12 h after that cooled to 0° C was added the mixture was extracted with Et2O fractions were washed with brine dried over Na2SO4 evaporated

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

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

Procedure: 452 mg (1.35 mmol) 4-(2-Cyanoethyl)-2-isobutylphenyl-trifluormethanesulfonate (6), 637.8 mg (1.70 mmol, 1.26 eq.) 2-(4-Methoxy-3-naphthalen-1-ylmethyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (64) and 236.8 mg (205 μmol, 0.15 eq.) Pd(Ph3P)4 were dissolved in 20 ml DME/EtOH (9+1). To this yellow solution 1.35 ml (2.70 mmol, 2 eq.) of a 2 M aq. Na2CO3-solution was added and the resulting mixture was heated at 80° C. for 15 h. After concentrating the mixture in vacuo the residue was taken up in water and extracted with CH2Cl2. The comb. org. fractions were dried over MgSO4 and evaporated. Column chromatography (hexanes/EtOAc (3+1)) yielded 513.8 mg (1.19 mmol, 87.78%) 3-(2-Isobutyl-4′-methoxy-3′-naphthalen-1-ylm Rf (hexanes/EtOAc (3+1))=0.40. 1H-NMR (500 MHz, CDCl3): δ=0.51 (d, 6H, J=6.62 Hz, 2*CH3), 1.42 (m, 1H, CH), 2.17 (d, 2H, J=7.25 Hz, CH2), 2.56 (t, 2H, J=7.41 Hz, CH2CH2CN), 2.87 (t, 2H, J=7.41 Hz, CH2CH2CN), 3.91 (s, 3H, OCH3), 4.42 (s, 2H, CH2Naphthyl), 6.71 (d, 1H, J=2.21 Hz), 6.94 (m, 3H), 7.00 (d, 1H, J=7.72 Hz), 7.04 (dd, 1H, J1=8.36 Hz, J2=2.36 Hz), 7.22 (m, 1H), 7.35 (m, 1H), 7.41 (m, 2H), 7.69 (d, 1H, J=8.20 Hz), 7.81 (m, 1H), 7.97 (m, 1H). MS (EI): m/z=434 (16), 433 (48), 336 (9), 335 (56), 294 (11), 293 (83), 292 (17), 277 (9), 265 (20), 264 (100), 253 (29). HR-MS (EI): Calcd. for C31H31NO: 433.240564. Found: 433.241264.

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

Procedure: 9.48 ml (152 mmol, 10 eqv) iodomethane was added to a suspension of 4.00 g (15.2 mmol) 2-Benzyl-4-bromo-phenol (20) and 10.50 g (76 mmol, 5 eqv) K2CO3 in 70 ml acetone and the resulting mixture was refluxed for 24 h. After adding water and aq. NH3-solution, the aq. layer was extracted with Et2O. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2) yielded 4.11 g (14.8 mmol, 98%) 21 as a colorless liquid: Rf (CH2Cl2) 0.77; 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.92 (s, 2H), 6.72 (d, 1H, J=8.59 Hz), 7.18 (m, 4H), 7.27 (m, 3H); LRMS (EI) m/z 279 (17), 278 (95), 277 (18), 276 (96), 263 (14), 261 (17), 198 (18), 197 (65), 182 (34), 181 (31), 166 (20), 165 (56), 154 (19), 153 (24), 152 (29), 92 (11), 91 (100), 77 (13), 76 (16), 63 (13); HRMS (EI) Calcd. for C14H13BrO: 276.014976. Found: 276.014234. the resulting mixture was refluxed for 24 h the aq. layer was extracted with Et2O fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: A solution of 13.24 g (99.3 mmol, 4.1 eqv) AlCl3 in 85 ml dry Et2O was added cautiously under stirring to a suspension of 3.91 g (102.9 mmol, 4.2 eqv) LiAlH4 in 100 ml dry Et2O. After complete addition the resulting mixture was stirred for 30 min at rt and then a solution of 6.85 g (24.5 mmol) 4-Bromo-2-(hydroxy-phenyl-methyl)-phenol (19) in 80 ml dry Et2O was added dropwise. The mixture was refluxed for 12 h and after that cooled to 0° C. After adding cautiously 60 ml of a mixture of Et2O/MeOH (1:1), 170 ml 1 N HCl-solution was added and the mixture was extracted with Et2O. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2) yielded 4.00 g (15.2 mmol, 62%) 20 as a colorless liquid: Rf (CH2Cl2) 0.41; 1H NMR (500 MHz, CDCl3) δ 3.95 (s, 2H), 4.64 (s, 1H), 6.67 (dd, 1H, J1=8.04 Hz, J2=0.79 Hz), 7.23 (m, 5H), 7.31 (m, 2H); LRMS (EI) m/z 265 (17), 264 (98), 263 (21), 262 (100), 186 (53), 184 (49), 183 (78), 182 (18), 181 (27), 165 (49), 153 (23), 152 (26), 91 (29), 84 (14), 78 (25), 77 (31), 76 (16), 63 (15); HRMS (EI) Calcd. for C13H11BrO: 261.999326. Found: 261.998568. After complete addition the resulting mixture The mixture was refluxed for 12 h after that cooled to 0° C was added the mixture was extracted with Et2O fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: 9.48 ml (152 mmol, 10 eqv) iodomethane was added to a suspension of 4.00 g (15.2 mmol) 2-Benzyl-4-bromo-phenol (20) and 10.50 g (76 mmol, 5 eqv) K2CO3 in 70 ml acetone and the resulting mixture was refluxed for 24 h. After adding water and aq. NH3-solution, the aq. layer was extracted with Et2O. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2) yielded 4.11 g (14.8 mmol, 98%) 21 as a colorless liquid: Rf (CH2Cl2) 0.77; 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 3H), 3.92 (s, 2H), 6.72 (d, 1H, J=8.59 Hz), 7.18 (m, 4H), 7.27 (m, 3H); LRMS (EI) m/z 279 (17), 278 (95), 277 (18), 276 (96), 263 (14), 261 (17), 198 (18), 197 (65), 182 (34), 181 (31), 166 (20), 165 (56), 154 (19), 153 (24), 152 (29), 92 (11), 91 (100), 77 (13), 76 (16), 63 (13); HRMS (EI) Calcd. for C14H13BrO: 276.014976. Found: 276.014234. the resulting mixture was refluxed for 24 h the aq. layer was extracted with Et2O fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: A solution of 13.24 g (99.3 mmol, 4.1 eqv) AlCl3 in 85 ml dry Et2O was added cautiously under stirring to a suspension of 3.91 g (102.9 mmol, 4.2 eqv) LiAlH4 in 100 ml dry Et2O. After complete addition the resulting mixture was stirred for 30 min at rt and then a solution of 6.85 g (24.5 mmol) 4-Bromo-2-(hydroxy-phenyl-methyl)-phenol (19) in 80 ml dry Et2O was added dropwise. The mixture was refluxed for 12 h and after that cooled to 0° C. After adding cautiously 60 ml of a mixture of Et2O/MeOH (1:1), 170 ml 1 N HCl-solution was added and the mixture was extracted with Et2O. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2) yielded 4.00 g (15.2 mmol, 62%) 20 as a colorless liquid: Rf (CH2Cl2) 0.41; 1H NMR (500 MHz, CDCl3) δ 3.95 (s, 2H), 4.64 (s, 1H), 6.67 (dd, 1H, J1=8.04 Hz, J2=0.79 Hz), 7.23 (m, 5H), 7.31 (m, 2H); LRMS (EI) m/z 265 (17), 264 (98), 263 (21), 262 (100), 186 (53), 184 (49), 183 (78), 182 (18), 181 (27), 165 (49), 153 (23), 152 (26), 91 (29), 84 (14), 78 (25), 77 (31), 76 (16), 63 (15); HRMS (EI) Calcd. for C13H11BrO: 261.999326. Found: 261.998568. After complete addition the resulting mixture The mixture was refluxed for 12 h after that cooled to 0° C was added the mixture was extracted with Et2O fractions were washed with brine dried over Na2SO4 evaporated