tert-butyl (2-formylphenyl) carbonate

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

Procedure: A solution of 18.5 grams (188 mmol, 2.2 eq) of trimethylsilylacetylene in 90 mL of dry THF was stirred under argon in a dry 500 mL round bottom flask at room temperature. To this solution was then slowly added 171 mL (171 mmol of a 1.0 M solution in THF, 2.0 eq) of ethyl magnesium bromide. The colorless solution was stirred for 2 hours. In a separate dry 1 L round bottom flask; 19.0 grams (85.5 mmol, 1.0 eq) of aldehyde 4 was dissolved in 270 mL of dry THF under argon. This solution was then cooled to −78° C. in an acetone/dry ice bath at which time 56.0 mL (89.7 mmol of a 1.6 M solution in Et2O, 1.05 eq) of methyl lithium was added with a syringe pump (2.5 mL/minute) and stirred at −78° C. for 25 minutes. The dry ice bath was then removed and the solution was stirred for 10 minutes at room temperature. The initial Grignard solution from the first flask was then added via cannula to the room temperature 1 L flask and the combined solutions were stirred for 2 hours under argon at room temperature. The solution was then diluted with Et2O and washed sequentially with 1.0 M HCl, saturated NaHCO3, brine and dried over MgSO4. The resulting colorless oil could be purified via silica gel chromatography (hexanes/EtOAc) or used directly in the subsequent step, Rf 0.29 (7:1 hexane:EtOAc). 1H-NMR (500 MHz, CDCl3): 7.16 (m, 2H), 6.89 (m, 2H), 6.18 (s, 1H), 3.89 (q, J=7.1 Hz, 1H), 1.51 (d, J=7.3 Hz, 3H), 0.20 (s, 9H). 13C-NMR (500 MHz, CDCl3): 154.02, 128.56, 128.41, 128.26, 121.15, 117.19, 108.45, 88.53, 29.24, 22.58, 0.16. IR (cm−1): 3447 (b), 2959 (w), 2163 (w), 1591 (w), 1453 (m), 1249 (s), 843 (s), 754 (s). HRMS (EI) calcd. for C13H18OSi: 218.1127. found: 218.1129. In a separate dry 1 L round bottom flask was added with a syringe pump (2.5 mL/minute) stirred at −78° C. for 25 minutes The dry ice bath was then removed the solution was stirred for 10 minutes at room temperature The initial Grignard solution from the first flask was then added via cannula to the room temperature 1 L flask the combined solutions were stirred for 2 hours under argon at room temperature The solution was then diluted with Et2O washed sequentially with 1.0 M HCl, saturated NaHCO3, brine dried over MgSO4 The resulting colorless oil could be purified via silica gel chromatography (hexanes/EtOAc)

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

Procedure: A solution of 18.5 grams (188 mmol, 2.2 eq) of trimethylsilylacetylene in 90 mL of dry THF was stirred under argon in a dry 500 mL round bottom flask at room temperature. To this solution was then slowly added 171 mL (171 mmol of a 1.0 M solution in THF, 2.0 eq) of ethyl magnesium bromide. The colorless solution was stirred for 2 hours. In a separate dry 1 L round bottom flask; 19.0 grams (85.5 mmol, 1.0 eq) of aldehyde 4 was dissolved in 270 mL of dry THF under argon. This solution was then cooled to −78° C. in an acetone/dry ice bath at which time 56.0 mL (89.7 mmol of a 1.6 M solution in Et2O, 1.05 eq) of methyl lithium was added with a syringe pump (2.5 mL/minute) and stirred at −78° C. for 25 minutes. The dry ice bath was then removed and the solution was stirred for 10 minutes at room temperature. The initial Grignard solution from the first flask was then added via cannula to the room temperature 1 L flask and the combined solutions were stirred for 2 hours under argon at room temperature. The solution was then diluted with Et2O and washed sequentially with 1.0 M HCl, saturated NaHCO3, brine and dried over MgSO4. The resulting colorless oil could be purified via silica gel chromatography (hexanes/EtOAc) or used directly in the subsequent step, Rf 0.29 (7:1 hexane:EtOAc). 1H-NMR (500 MHz, CDCl3): 7.16 (m, 2H), 6.89 (m, 2H), 6.18 (s, 1H), 3.89 (q, J=7.1 Hz, 1H), 1.51 (d, J=7.3 Hz, 3H), 0.20 (s, 9H). 13C-NMR (500 MHz, CDCl3): 154.02, 128.56, 128.41, 128.26, 121.15, 117.19, 108.45, 88.53, 29.24, 22.58, 0.16. IR (cm−1): 3447 (b), 2959 (w), 2163 (w), 1591 (w), 1453 (m), 1249 (s), 843 (s), 754 (s). HRMS (EI) calcd. for C13H18OSi: 218.1127. found: 218.1129. In a separate dry 1 L round bottom flask was added with a syringe pump (2.5 mL/minute) stirred at −78° C. for 25 minutes The dry ice bath was then removed the solution was stirred for 10 minutes at room temperature The initial Grignard solution from the first flask was then added via cannula to the room temperature 1 L flask the combined solutions were stirred for 2 hours under argon at room temperature The solution was then diluted with Et2O washed sequentially with 1.0 M HCl, saturated NaHCO3, brine dried over MgSO4 The resulting colorless oil could be purified via silica gel chromatography (hexanes/EtOAc)

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

Procedure: 21.5 g (93.8 mmol) of 2-(tert-butoxycarbonyloxy)-benzaldehyde and 80 ml (750 mmol) of 2-methyl-2-butene are diluted in 250 ml of tert-butanol. A solution containing 28.1 g (234 mmol) of sodium hydrogenphosphate and 29.7 g (328 mmol) of sodium chlorite in 75 ml of water is added dropwise to the reaction medium, which is stirred at ambient temperature for 2 hours. The mixture is evaporated under reduced pressure and the residue is dissolved in dichloromethane. The organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated. The white solid obtained is precipitated from heptane at 0° C. The precipitate is filtered off and then rinsed with heptane and dried. 15.8 g of 2-(tert-butoxycarbonyloxy)benzoic acid are obtained in the form of a white powder with a yield of 70%. is added dropwise to the reaction medium, which The mixture is evaporated under reduced pressure the residue is dissolved in dichloromethane The organic phase is washed with water dried over magnesium sulphate filtered concentrated The white solid obtained is precipitated from heptane at 0° C The precipitate is filtered off rinsed with heptane dried

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

Procedure: 21.5 g (93.8 mmol) of 2-(tert-butoxycarbonyloxy)-benzaldehyde and 80 ml (750 mmol) of 2-methyl-2-butene are diluted in 250 ml of tert-butanol. A solution containing 28.1 g (234 mmol) of sodium hydrogenphosphate and 29.7 g (328 mmol) of sodium chlorite in 75 ml of water is added dropwise to the reaction medium, which is stirred at ambient temperature for 2 hours. The mixture is evaporated under reduced pressure and the residue is dissolved in dichloromethane. The organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated. The white solid obtained is precipitated from heptane at 0° C. The precipitate is filtered off and then rinsed with heptane and dried. 15.8 g of 2-(tert-butoxycarbonyloxy)benzoic acid are obtained in the form of a white powder with a yield of 70%. is added dropwise to the reaction medium, which The mixture is evaporated under reduced pressure the residue is dissolved in dichloromethane The organic phase is washed with water dried over magnesium sulphate filtered concentrated The white solid obtained is precipitated from heptane at 0° C The precipitate is filtered off rinsed with heptane dried

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

Procedure: 350 mg (2.8 mmol) of N,N-dimethylaminopyridine and 8.1 ml (46.9 mmol) of N,N-diisopropylethylamine are added to a solution containing 20.9 g (95.7 mmol) of di(tert-butyl)dicarbonate in 150 ml of tetrahydrofuran under a stream of nitrogen. 10 ml (93.8 mmol) of salicylaldehyde are added dropwise. After stirring at ambient temperature for 2 hours, the medium is treated with a 1N aqueous hydrochloric acid solution and then extracted with a heptane/ethyl acetate 1/1 mixture. The organic phase is dried over magnesium sulphate, filtered and concentrated. 21.5 g of 2-(tert-butoxycarbonyloxy)benzaldehyde are obtained in the form of a yellow oil with a quantitative yield. extracted with a heptane/ethyl acetate 1/1 mixture The organic phase is dried over magnesium sulphate filtered concentrated

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

Procedure: A solution of 18.5 grams (188 mmol, 2.2 eq) of trimethylsilylacetylene in 90 mL of dry THF was stirred under argon in a dry 500 mL round bottom flask at room temperature. To this solution was then slowly added 171 mL (171 mmol of a 1.0 M solution in THF, 2.0 eq) of ethyl magnesium bromide. The colorless solution was stirred for 2 hours. In a separate dry 1 L round bottom flask; 19.0 grams (85.5 mmol, 1.0 eq) of aldehyde 4 was dissolved in 270 mL of dry THF under argon. This solution was then cooled to −78° C. in an acetone/dry ice bath at which time 56.0 mL (89.7 mmol of a 1.6 M solution in Et2O, 1.05 eq) of methyl lithium was added with a syringe pump (2.5 mL/minute) and stirred at −78° C. for 25 minutes. The dry ice bath was then removed and the solution was stirred for 10 minutes at room temperature. The initial Grignard solution from the first flask was then added via cannula to the room temperature 1 L flask and the combined solutions were stirred for 2 hours under argon at room temperature. The solution was then diluted with Et2O and washed sequentially with 1.0 M HCl, saturated NaHCO3, brine and dried over MgSO4. The resulting colorless oil could be purified via silica gel chromatography (hexanes/EtOAc) or used directly in the subsequent step, Rf 0.29 (7:1 hexane:EtOAc). 1H-NMR (500 MHz, CDCl3): 7.16 (m, 2H), 6.89 (m, 2H), 6.18 (s, 1H), 3.89 (q, J=7.1 Hz, 1H), 1.51 (d, J=7.3 Hz, 3H), 0.20 (s, 9H). 13C-NMR (500 MHz, CDCl3): 154.02, 128.56, 128.41, 128.26, 121.15, 117.19, 108.45, 88.53, 29.24, 22.58, 0.16. IR (cm−1): 3447 (b), 2959 (w), 2163 (w), 1591 (w), 1453 (m), 1249 (s), 843 (s), 754 (s). HRMS (EI) calcd. for C13H18OSi: 218.1127. found: 218.1129. In a separate dry 1 L round bottom flask was added with a syringe pump (2.5 mL/minute) stirred at −78° C. for 25 minutes The dry ice bath was then removed the solution was stirred for 10 minutes at room temperature The initial Grignard solution from the first flask was then added via cannula to the room temperature 1 L flask the combined solutions were stirred for 2 hours under argon at room temperature The solution was then diluted with Et2O washed sequentially with 1.0 M HCl, saturated NaHCO3, brine dried over MgSO4 The resulting colorless oil could be purified via silica gel chromatography (hexanes/EtOAc)

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

Procedure: 21.5 g (93.8 mmol) of 2-(tert-butoxycarbonyloxy)-benzaldehyde and 80 ml (750 mmol) of 2-methyl-2-butene are diluted in 250 ml of tert-butanol. A solution containing 28.1 g (234 mmol) of sodium hydrogenphosphate and 29.7 g (328 mmol) of sodium chlorite in 75 ml of water is added dropwise to the reaction medium, which is stirred at ambient temperature for 2 hours. The mixture is evaporated under reduced pressure and the residue is dissolved in dichloromethane. The organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated. The white solid obtained is precipitated from heptane at 0° C. The precipitate is filtered off and then rinsed with heptane and dried. 15.8 g of 2-(tert-butoxycarbonyloxy)benzoic acid are obtained in the form of a white powder with a yield of 70%. is added dropwise to the reaction medium, which The mixture is evaporated under reduced pressure the residue is dissolved in dichloromethane The organic phase is washed with water dried over magnesium sulphate filtered concentrated The white solid obtained is precipitated from heptane at 0° C The precipitate is filtered off rinsed with heptane dried

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

Procedure: 350 mg (2.8 mmol) of N,N-dimethylaminopyridine and 8.1 ml (46.9 mmol) of N,N-diisopropylethylamine are added to a solution containing 20.9 g (95.7 mmol) of di(tert-butyl)dicarbonate in 150 ml of tetrahydrofuran under a stream of nitrogen. 10 ml (93.8 mmol) of salicylaldehyde are added dropwise. After stirring at ambient temperature for 2 hours, the medium is treated with a 1N aqueous hydrochloric acid solution and then extracted with a heptane/ethyl acetate 1/1 mixture. The organic phase is dried over magnesium sulphate, filtered and concentrated. 21.5 g of 2-(tert-butoxycarbonyloxy)benzaldehyde are obtained in the form of a yellow oil with a quantitative yield. extracted with a heptane/ethyl acetate 1/1 mixture The organic phase is dried over magnesium sulphate filtered concentrated