[1-(溴甲基)环丙基]甲氧基甲基苯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 58.9 g of 1-benzyloxymethyl-1-(hydroxymethyl)cyclopropane and 88.5 g of triphenylphosphine are dissolved in 600 ml of methylene chloride, and 60 g of N-bromosuccinimide are added in portions at 0° C. The reaction mixture is stirred at room temperature for 16 h and concentrated and the residue is purified by means of FC over 3 kg of silica gel with a 1:1 mixture of methylene chloride and hexane as the eluting agent. This gives 68 g of the pure title compound: Rf (1:1 mixture from methylene chloride and hexane)=0.50. concentrated the residue is purified by means of FC over 3 kg of silica gel with a 1:1 mixture of methylene chloride and hexane as the eluting agent

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-(2,4-Diamino-pyrimidin-5-ylmethyl)-6-ethoxy-4′-methoxymethoxy-biphenyl-2-ol (2.5 g; 6.31 mmol) is dissolved in dimethylformamide (125 ml; dried over a molecular sieve) and potassium tert-butylate (920 mg; 8.2 mmol) is added at room temperature. A solution of [(1-bromomethyl-cyclopropyl)methoxymethyl]-benzene (2.253 g; 8.83 mmol) in dimethylformamide (3 ml) is then added and the mixture is stirred for 100 minutes at a bath temperature of 60° C. The reaction mixture is concentrated, diluted with water (100 ml) and extracted with methylene chloride (120 ml) and re-extracted (50 ml). The combined organic phases are concentrated and the residue is chromatographed over silica gel (300 g) with methylene chloride/methanol/NH4OH conc. (19/1/0.05). The combined pure fractions are concentrated and the residue is dissolved in acetic acid conc. (40 ml) and ethanol (10 ml) and hydrogenated over Pd/C 10% (900 mg). The reaction mixture is filtered with suction and the filtrate is concentrated. The residue is stirred with water (50 ml) and the pH is adjusted to approx. 10 by addition of NH4OH conc. The product which has precipitated out is filtered off with suction and the residue is washed with a little water and dried under a high vacuum. 2.24 g (95%) {1-[4-(2,4-diamino-pyrimidin-5-ylmethyl)-6-ethoxy-4′-methoxymethoxy-biphenyl-2-yloxymethyl]-cyclopropyl}-methanol are obtained as a colourless powder. is added at room temperature The reaction mixture is concentrated diluted with water (100 ml) extracted with methylene chloride (120 ml) re-extracted (50 ml) The combined organic phases are concentrated the residue is chromatographed over silica gel (300 g) with methylene chloride/methanol/NH4OH conc. (19/1/0.05) The combined pure fractions are concentrated the residue is dissolved in acetic acid conc. (40 ml) The reaction mixture is filtered with suction the filtrate is concentrated The residue is stirred with water (50 ml) by addition of NH4OH conc. The product which has precipitated out is filtered off with suction the residue is washed with a little water dried under a high vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 58.9 g of 1-benzyloxymethyl-1-(hydroxymethyl)cyclopropane and 88.5 g of triphenylphosphine are dissolved in 600 ml of methylene chloride, and 60 g of N-bromosuccinimide are added in portions at 0° C. The reaction mixture is stirred at room temperature for 16 h and concentrated and the residue is purified by means of FC over 3 kg of silica gel with a 1:1 mixture of methylene chloride and hexane as the eluting agent. This gives 68 g of the pure title compound: Rf (1:1 mixture from methylene chloride and hexane)=0.50. concentrated the residue is purified by means of FC over 3 kg of silica gel with a 1:1 mixture of methylene chloride and hexane as the eluting agent