2,4-dichloro-N-methoxy-N-methylbenzamide

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: To the solution of 85 mL of diisopropylamine (Fluka 38300) and 2.5 L of THF at −75° C. under Argon is added 370 mL (0.55 Mol) of butyl lithium (BuLi; 1.6N in hexanes; Fluka 20160) within 1 h. To this is added 71 g (0.5 Mol) of 4-methyl-2-methylsulfanyl-pyrimidine in 250 mL of CH2Cl2 at −75° C. within 30 min. After this, a solution of 118 g (0.5 Mol) of 2,4dichloro-N-methoxy-N-methyl-benzamide in 250 mL of CH2Cl2 at −75° C. within 30 min followed by letting the mixture warn up to rt. After completion, the reaction mixture is poured onto 7 L of NH4Cl satd. and extracted with ethyl acetate. The combined organic layers are washed with brine, dried and evaporated. The crude product is suspended in hexanes. After filtering off and drying 1-(2,4-dichloro-phenyl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone is obtained as yellow crystals. Title compound: m.p.: 105-107° C.; ES-MS: 313.0/314.9 [M+H]+. warn up to rt and extracted with ethyl acetate The combined organic layers are washed with brine dried evaporated After filtering off drying 1-(2,4-dichloro-phenyl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone is obtained as yellow crystals

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

実験手順: A mixture of 32.6 g of N-methoxymethanamine hydrochloride and 91.2 ml of triethylamine in 500 ml of DCM is cooled in an ice bath, and then 47 ml of 2,4-dichlorobenzoyl chloride are added slowly and the mixture is left to stir while allowing the temperature to rise to AT. After stirring for 1 hour at AT, water is added to the reaction mixture, the mixture is extracted with DCM, the organic phase is dried over Na2SO4 and the solvent is evaporated under vacuum. 53 g of the expected compound are obtained. is cooled in an ice bath the mixture is left is added to the reaction mixture the mixture is extracted with DCM the organic phase is dried over Na2SO4 the solvent is evaporated under vacuum

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

実験手順: To a stirring hazy solution of 2,4-dichloro-N-methoxy-N-methylbenzenecarboxamide (1 g, 4.27 mmol), in THF (20 ml) is added BuLi (2.051 ml, 5.13 mmol) in portions. The reaction is stirred for 4 hours at RT and the partitioned between 1M HCl (100 ml) and EtOAc (140 ml). The organic portion is washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude product is purified by ISCO combiflash chromatography eluting with 0 to 100% EtOAc/iso-hexane on a 40 g silica-column to yield 1-(2,4-dichloro-phenyl)-pentan-1-one as a brown oil; 1H NMR (400 MHz, CDCl3) δ 7.45 (1H, d, J 2.0), 7.43 (1H, d, J 7.3), 7.32 (1H, dd, J 7.3, 2.0), 2.94 (2H, t, J 7.4), 1.70 (2H, m), 1.40 (2H, m), 0.95 (3H, t, J 7.3). the partitioned between 1M HCl (100 ml) and EtOAc (140 ml) The organic portion is washed with brine dried over Na2SO4 concentrated in vacuo The crude product is purified by ISCO combiflash chromatography eluting with 0 to 100% EtOAc/iso-hexane on a 40 g silica-column

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

実験手順: To the solution of 85 mL of diisopropylamine (Fluka 38300) and 2.5 L of THF at −75° C. under Argon is added 370 mL (0.55 Mol) of butyl lithium (BuLi; 1.6N in hexanes; Fluka 20160) within 1 h. To this is added 71 g (0.5 Mol) of 4-methyl-2-methylsulfanyl-pyrimidine in 250 mL of CH2Cl2 at −75° C. within 30 min. After this, a solution of 118 g (0.5 Mol) of 2,4dichloro-N-methoxy-N-methyl-benzamide in 250 mL of CH2Cl2 at −75° C. within 30 min followed by letting the mixture warn up to rt. After completion, the reaction mixture is poured onto 7 L of NH4Cl satd. and extracted with ethyl acetate. The combined organic layers are washed with brine, dried and evaporated. The crude product is suspended in hexanes. After filtering off and drying 1-(2,4-dichloro-phenyl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone is obtained as yellow crystals. Title compound: m.p.: 105-107° C.; ES-MS: 313.0/314.9 [M+H]+. warn up to rt and extracted with ethyl acetate The combined organic layers are washed with brine dried evaporated After filtering off drying 1-(2,4-dichloro-phenyl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone is obtained as yellow crystals

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

実験手順: A mixture of 32.6 g of N-methoxymethanamine hydrochloride and 91.2 ml of triethylamine in 500 ml of DCM is cooled in an ice bath, and then 47 ml of 2,4-dichlorobenzoyl chloride are added slowly and the mixture is left to stir while allowing the temperature to rise to AT. After stirring for 1 hour at AT, water is added to the reaction mixture, the mixture is extracted with DCM, the organic phase is dried over Na2SO4 and the solvent is evaporated under vacuum. 53 g of the expected compound are obtained. is cooled in an ice bath the mixture is left is added to the reaction mixture the mixture is extracted with DCM the organic phase is dried over Na2SO4 the solvent is evaporated under vacuum