2-Di-t-butylphosphino-2'-(N,N-dimethylamino))-1,1'-biphenyl

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 14.6 g (60.5 mmol) of 4-bromo-1-methoxy-2-methylindane, 10.8 g (60.5 mmol) of 1-methoxy-2-methyl-4-indanol, 38.5 g (181 mmol) K3PO4, and 200 ml of toluene, a mixture of 696 mg (1.21 mmol) Pd(dba)2 and 825 mg (2.42 mmol) of 2-di(tert-butyl)phosphino-2′-(N,N-dimethylamino)biphenyl was added under an argon atmosphere. This mixture was stirred for 14 hours at 100° C. Then, 300 ml of water was added. The organic layer was separated, and the aqueous layer was extracted with 3×100 ml of CH2Cl2. The combined extract was washed with 2×100 ml of water, dried over K2CO3, and evaporated to dryness. The analytically pure product was obtained using flash chromatography on Silica Gel 60 (40-63 μm, d 50 mm, l 400 mm, eluant: hexanes-dichloromethane=1:1, vol.). Yield, 12.4 g (61%). On the evidence of NMR spectra, the product consists of a mixture of isomers. was added under an argon atmosphere The organic layer was separated the aqueous layer was extracted with 3×100 ml of CH2Cl2 The combined extract was washed with 2×100 ml of water dried over K2CO3 evaporated to dryness The analytically pure product was obtained Yield On the evidence of NMR spectra, the product consists of a mixture of isomers

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 14.6 g (60.5 mmol) of 4-bromo-1-methoxy-2-methylindane, 10.8 g (60.5 mmol) of 1-methoxy-2-methyl-4-indanol, 38.5 g (181 mmol) K3PO4, and 200 ml of toluene, a mixture of 696 mg (1.21 mmol) Pd(dba)2 and 825 mg (2.42 mmol) of 2-di(tert-butyl)phosphino-2′-(N,N-dimethylamino)biphenyl was added under an argon atmosphere. This mixture was stirred for 14 hours at 100° C. Then, 300 ml of water was added. The organic layer was separated, and the aqueous layer was extracted with 3×100 ml of CH2Cl2. The combined extract was washed with 2×100 ml of water, dried over K2CO3, and evaporated to dryness. The analytically pure product was obtained using flash chromatography on Silica Gel 60 (40-63 μm, d 50 mm, l 400 mm, eluant: hexanes-dichloromethane=1:1, vol.). Yield, 12.4 g (61%). On the evidence of NMR spectra, the product consists of a mixture of isomers. was added under an argon atmosphere The organic layer was separated the aqueous layer was extracted with 3×100 ml of CH2Cl2 The combined extract was washed with 2×100 ml of water dried over K2CO3 evaporated to dryness The analytically pure product was obtained Yield On the evidence of NMR spectra, the product consists of a mixture of isomers

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-[2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (0.051 g, 0.12 mmol), phenol (0.017 g, 0.18 mmol), potassium phosphate (0.056 g, 0.26 mmol), 2-di-tert-butylphosphino-2′-(N,N-dimethylamino)biphenyl (0.0041 g, 0.012 mmol) and Pd(OAc)2 (0.002 g, 0.009 mmol) in 1 mL of toluene was stirred at 100° C. for 13 h, then at 150° C. for 4 h. The resulting dark orange mixture was partitioned between 10 mL of ethyl acetate and 10 mL of water. The organic layer was dried over MgSO4, filtered and concentrated to an orange oil. Column chromatography (0-20% EtOAc/hexanes) afforded 0.032 g (62%) of impure 2,2-dimethyl-1-[2-phenoxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one as a yellow oil, which was used without further purification. at 150° C. for 4 h The resulting dark orange mixture was partitioned between 10 mL of ethyl acetate and 10 mL of water The organic layer was dried over MgSO4 filtered concentrated to an orange oil

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-[2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (0.051 g, 0.12 mmol), phenol (0.017 g, 0.18 mmol), potassium phosphate (0.056 g, 0.26 mmol), 2-di-tert-butylphosphino-2′-(N,N-dimethylamino)biphenyl (0.0041 g, 0.012 mmol) and Pd(OAc)2 (0.002 g, 0.009 mmol) in 1 mL of toluene was stirred at 100° C. for 13 h, then at 150° C. for 4 h. The resulting dark orange mixture was partitioned between 10 mL of ethyl acetate and 10 mL of water. The organic layer was dried over MgSO4, filtered and concentrated to an orange oil. Column chromatography (0-20% EtOAc/hexanes) afforded 0.032 g (62%) of impure 2,2-dimethyl-1-[2-phenoxy-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one as a yellow oil, which was used without further purification. at 150° C. for 4 h The resulting dark orange mixture was partitioned between 10 mL of ethyl acetate and 10 mL of water The organic layer was dried over MgSO4 filtered concentrated to an orange oil

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 14.6 g (60.5 mmol) of 4-bromo-1-methoxy-2-methylindane, 10.8 g (60.5 mmol) of 1-methoxy-2-methyl-4-indanol, 38.5 g (181 mmol) K3PO4, and 200 ml of toluene, a mixture of 696 mg (1.21 mmol) Pd(dba)2 and 825 mg (2.42 mmol) of 2-di(tert-butyl)phosphino-2′-(N,N-dimethylamino)biphenyl was added under an argon atmosphere. This mixture was stirred for 14 hours at 100° C. Then, 300 ml of water was added. The organic layer was separated, and the aqueous layer was extracted with 3×100 ml of CH2Cl2. The combined extract was washed with 2×100 ml of water, dried over K2CO3, and evaporated to dryness. The analytically pure product was obtained using flash chromatography on Silica Gel 60 (40-63 μm, d 50 mm, l 400 mm, eluant: hexanes-dichloromethane=1:1, vol.). Yield, 12.4 g (61%). On the evidence of NMR spectra, the product consists of a mixture of isomers. was added under an argon atmosphere The organic layer was separated the aqueous layer was extracted with 3×100 ml of CH2Cl2 The combined extract was washed with 2×100 ml of water dried over K2CO3 evaporated to dryness The analytically pure product was obtained Yield On the evidence of NMR spectra, the product consists of a mixture of isomers

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 14.6 g (60.5 mmol) of 4-bromo-1-methoxy-2-methylindane, 10.8 g (60.5 mmol) of 1-methoxy-2-methyl-4-indanol, 38.5 g (181 mmol) K3PO4, and 200 ml of toluene, a mixture of 696 mg (1.21 mmol) Pd(dba)2 and 825 mg (2.42 mmol) of 2-di(tert-butyl)phosphino-2′-(N,N-dimethylamino)biphenyl was added under an argon atmosphere. This mixture was stirred for 14 hours at 100° C. Then, 300 ml of water was added. The organic layer was separated, and the aqueous layer was extracted with 3×100 ml of CH2Cl2. The combined extract was washed with 2×100 ml of water, dried over K2CO3, and evaporated to dryness. The analytically pure product was obtained using flash chromatography on Silica Gel 60 (40-63 μm, d 50 mm, 1 400 mm, eluant:hexanes-dichloromethane=1:1, vol.). Yield 12.4 g (61%). On the evidence of NMR spectra, the product consists of a mixture of isomers. was added under an argon atmosphere The organic layer was separated the aqueous layer was extracted with 3×100 ml of CH2Cl2 The combined extract was washed with 2×100 ml of water dried over K2CO3 evaporated to dryness The analytically pure product was obtained On the evidence of NMR spectra, the product consists of a mixture of isomers

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 14.6 g (60.5 mmol) of 4-bromo-1-methoxy-2-methylindane, 10.8 g (60.5 mmol) of 1-methoxy-2-methyl-4-indanol, 38.5 g (181 mmol) K3PO4, and 200 ml of toluene, a mixture of 696 mg (1.21 mmol) Pd(dba)2 and 825 mg (2.42 mmol) of 2-di(tert-butyl)phosphino-2′-(N,N-dimethylamino)biphenyl was added under an argon atmosphere. This mixture was stirred for 14 hours at 100° C. Then, 300 ml of water was added. The organic layer was separated, and the aqueous layer was extracted with 3×100 ml of CH2Cl2. The combined extract was washed with 2×100 ml of water, dried over K2CO3, and evaporated to dryness. The analytically pure product was obtained using flash chromatography on Silica Gel 60 (40-63 μm, d 50 mm, 1 400 mm, eluant:hexanes-dichloromethane=1:1, vol.). Yield 12.4 g (61%). On the evidence of NMR spectra, the product consists of a mixture of isomers. was added under an argon atmosphere The organic layer was separated the aqueous layer was extracted with 3×100 ml of CH2Cl2 The combined extract was washed with 2×100 ml of water dried over K2CO3 evaporated to dryness The analytically pure product was obtained On the evidence of NMR spectra, the product consists of a mixture of isomers

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon atmosphere, to a mixture of 5.50 g (15.6 mmol) of 4-bromo-1-(1-naphthyl)-2,3-dihydro-1H-inden-1-yl methyl ether, 4.00 g (15.5 mmol) of 3-(1-naphthyl)-1H-inden-7-ol, 6.60 g (31.1 mmol) of K3PO4, and 150 ml of toluene, a mixture of 183 mg (0.32 mmol) of Pd(dba)2 and 212 mg (0.62 mmol) of N-{2′-[di(tert-butyl)phosphino][1,1′-biphenyl]-2-yl}-N,N-dimethylamine was added. The resulting mixture was stirred for 8 hours at 100° C. Then, 300 ml of water was added, the organic layer was separated, and the aqueous layer was extracted with 3×75 ml of CH2Cl2. The combined extract was dried over Na2SO4 and evaporated to dryness. The crude 1-(1-methoxy-4-{[1-methoxy-1-(1-naphthyl)-2,3-dihydro-1H-inden-4-yl]oxy}-2,3-dihydro-1H-inden-1-yl)naphthalene was purified using a short column with Silica Gel 60 (40-63 μm, d 50 mm, l 70 mm, eluant: CH2Cl2). This product was demethoxylated in a mixture of 170 ml of 16 M HCl and 170 ml of methanol for 7 hours at reflux. The crude product was extracted with 3×150 ml of CH2Cl2. The combined extract was washed with 2×100 ml of water, dried over K2CO3, and evaporated to dryness. The analytically pure product was obtained by flash chromatography on Silica Gel 60 (40-63 μm, d 35 mm, l 300 mm, eluant:hexanes-CH2Cl2=5:1). Yield, 2.65 g (34%) of a white solid. was added the organic layer was separated the aqueous layer was extracted with 3×75 ml of CH2Cl2 The combined extract was dried over Na2SO4 evaporated to dryness The crude 1-(1-methoxy-4-{[1-methoxy-1-(1-naphthyl)-2,3-dihydro-1H-inden-4-yl]oxy}-2,3-dihydro-1H-inden-1-yl)naphthalene was purified This product was demethoxylated in a mixture of 170 ml of 16 M HCl and 170 ml of methanol for 7 hours at reflux The crude product was extracted with 3×150 ml of CH2Cl2 The combined extract was washed with 2×100 ml of water dried over K2CO3 evaporated to dryness The analytically pure product was obtained by flash chromatography on Silica Gel 60 (40-63 μm, d 35 mm, l 300 mm, eluant:hexanes-CH2Cl2=5:1) Yield