1,3-dichloro-5-(chloromethyl)benzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Sodium metal (1.01 g, 44 mmol) was added to ethanol (100 ml) and stirred until all the metal had dissolved. Ethylacetoacetate (15.6 g, 111 mmol) was added and the reaction mixture was stirred under a nitrogen atmosphere for 10 minutes. 3,5-dichlorobenzyl chloride (7.24 g, 40 mmol) was added and the reaction mixture was stirred at room temperature for 3 days. The reaction mixture was filtered and the solution was concentrated under reduced pressure. The orange oil was purified by flash chromatography on silica gel eluting with pentane followed by pentane:ethyl acetate (30:1, by volume) to afford the title compound as a colourless oil (6.4 g). had dissolved the reaction mixture was stirred under a nitrogen atmosphere for 10 minutes the reaction mixture was stirred at room temperature for 3 days The reaction mixture was filtered the solution was concentrated under reduced pressure The orange oil was purified by flash chromatography on silica gel eluting with pentane

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

実験手順: To a stirred solution of N-t-butoxycarbonyl-D-serine (10.0 g, 48.7 mol) in N,N-dimethylformamide (150 mL) at about 0° C. was added sodium hydride (4.0 g, 60% dispersion in mineral oil, 99.84 mmol) portionwise. The mixture was stirred for about 30 minutes, and then a solution of 1,3-dichloro-5-chloromethyl-benzene (9.5 mL, 48.7 mmol) in ethyl ether (40 mL) was added. The reaction was allowed to slowly warm to room temperature overnight. The reaction was then quenched with 1N NaOH, the mixture extracted three times with dichloromethane. The combined organic layers were then washed three times with water, 1N, HCl, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give crude product. The original basic aqueous layer was then acidified to about pH 4 with HCl, and the mixture was extracted three times with dichloromethane. These three organic layers were combined and washed three times each with water and brine then dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give an additional 620 mg of crude product. Both product fractions were combined and purified by silica gel chromatography using 5% methanol/chloroform as eluent and yielded the title compound of part 1-E (12.39 g, 70%): −APcl MS (M−1)− 363, (M−3)− 361; 1H NMR=400 MHz (CDCl3) δ: 7.13 (arom, s, 3H), 5.42 (NH, d, 1H), 4.50 (CHCO2H, m, 1H), 4.45 (PhCH2O, s, 2H), 3.82 (CH2OBz, d of d, 2H), 1.43 (BOC, s, 9H). The reaction was then quenched with 1N NaOH the mixture extracted three times with dichloromethane The combined organic layers were then washed three times with water, 1N, HCl dried over anhydrous magnesium sulfate filtered concentrated in vacuo to give crude product the mixture was extracted three times with dichloromethane washed three times each with water and brine then dried over anhydrous magnesium sulfate filtered concentrated in vacuo to give an additional 620 mg of crude product purified by silica gel chromatography

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

実験手順: To a vigorously stirred solution of 3,5-dichlorobenzylchloride (28 g) in dichloromethane (150 ml) was added a mixture of KCN (27.5 g) and tetrabutylammonium hydrogen sulphate (2.38 g) in water (110 ml). After stirring at room temperature for 22 hours, the mixture was diluted with dichloromethane, the organic phase washed with water and concentrated in vacuo to leave an oil. Filtration through silica with toluene followed by concentration then trituration with hexane gave the desired product as a colourless solid. 15.8 g, mp. 31°-32° C. the organic phase washed with water concentrated in vacuo to leave an oil Filtration through silica with toluene followed by concentration

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

実験手順: A mixture of 3,5-dichlorobenzyl alcohol (Aldrich, 25 g), thionyl chloride (100 ml) and DMF (0.5 ml) was stirred and refluxed for 4 hours. After cooling the mixture was concentrated in vacuo, the residue was taken up in ether, washed with saturated aqueous NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo to give 3,5-dichlorobenzyl chloride as a light yellow solid, which was used without further purification, 28 g, mp. 32°-36° C. refluxed for 4 hours After cooling the mixture was concentrated in vacuo washed with saturated aqueous NaHCO3 and brine dried (MgSO4) concentrated in vacuo

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

実験手順: To a vigorously stirred solution of 3,5-dichlorobenzylchloride (28 g) in dichloromethane (150 ml) was added a mixture of KCN (27.5 g) and tetrabutylammonium hydrogen sulphate (2.38 g) in water (110 ml). After stirring at room temperature for 22 hours, the mixture was diluted with dichloromethane, the organic phase washed with water and concentrated in vacuo to leave an oil. Filtration through silica with toluene followed by concentration then trituration with hexane gave the desired product as a colourless solid. 15.8 g, mp. 31°-32° C. the organic phase washed with water concentrated in vacuo to leave an oil Filtration through silica with toluene followed by concentration

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

実験手順: A mixture of 3,5-dichlorobenzyl alcohol (Aldrich, 25 g) , thionyl chloride (100 ml) and DMF (0.5 ml) was stirred and refluxed for 4 hours. After cooling the mixture was concentrated in vacuo, the residue was taken up in ether, washed with saturated aqueous NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo to give 3,5-dichlorobenzyl chloride as a light yellow solid, which was used without further purification, 28 g, mp. 32°-36° C. refluxed for 4 hours After cooling the mixture was concentrated in vacuo washed with saturated aqueous NaHCO3 and brine dried (MgSO4) concentrated in vacuo

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

実験手順: To a vigorously stirred solution of 3,5-dichlorobenzylchloride (28 g) in dichloromethane (150 ml) was added a mixture of KCN (27.5 g) and tetrabutylammonium hydrogen sulphate (2.38 g) in water (110 ml). After stirring at room temperature for 22 hours, the mixture was diluted with dichloromethane, the organic phase washed with water and concentrated in vacuo to leave an oil. Filtration through silica with toluene followed by concentration then trituration with hexane gave the desired product as a colourless solid. 15.8 g, mp. 31°-32° C. the organic phase washed with water concentrated in vacuo to leave an oil Filtration through silica with toluene followed by concentration