N-methoxy-N-methylcarbamoyl chloride

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

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

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

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

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

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

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

Procedure: 1.5 g of 4-(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy)aniline was dissolved in 20 ml of N,N-dimethylformamide, and 0.8 g of N-methoxy-N-methylcarbamoyl chloride was gradually added to this solution at room temperature. After 1.5 hours, N,N-dimethylformamide was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, washed with water and dried over magnesium sulfate. After distilling off the solvent, the residual oily substance was purified by silica gel column chromatography by using a solvent mixture of ethyl acetate/n-hexane=1/4 as the developer, to obtain 1.4 g of compound No. 2 as identified in Table 1. N,N-dimethylformamide was distilled off under reduced pressure The residue was dissolved in ethyl acetate washed with water dried over magnesium sulfate After distilling off the solvent the residual oily substance was purified by silica gel column chromatography a solvent mixture of ethyl acetate/n-hexane=1/4 as the developer

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

Procedure: 1.5 g of 4-(2,3-dihydro-2,2-dimethyl-7-benzofuranyloxy)aniline was dissolved in 20 ml of N,N-dimethylformamide, and 0.8 g of N-methoxy-N-methylcarbamoyl chloride was gradually added to this solution at room temperature. After 1.5 hours, N,N-dimethylformamide was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, washed with water and dried over magnesium sulfate. After distilling off the solvent, the residual oily substance was purified by silica gel column chromatography by using a solvent mixture of ethyl acetate/n-hexane=1/4 as the developer, to obtain 1.4 g of compound No. 2 as identified in Table 1. N,N-dimethylformamide was distilled off under reduced pressure The residue was dissolved in ethyl acetate washed with water dried over magnesium sulfate After distilling off the solvent the residual oily substance was purified by silica gel column chromatography a solvent mixture of ethyl acetate/n-hexane=1/4 as the developer

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

Procedure: 6.5 g of 4-(2,3-dihydro-2,2-dimethyl-5-benzofuranyloxy)aniline was dissolved in 30 ml of pyridine, and 3.8 g of N-methoxy-N-methylcarbamoyl chloride was gradually dropwise added thereto over a period of 30 minutes under cooling with ice. Stirring was continued for 1.5 hours, and then pyridine was distilled off under reduced pressure. The residual oily substance was dissolved in 100 ml of toluene, and washed sequentially with water, a dilute hydrochloric acid aqueous solution and a saturated sodium chloride aqueous solution. Then, toluene was distilled off. The residue was purified by silica gel column chromatography by using a solvent mixture of ethyl acetate/n-hexane=1/3 as the developer, to obtain 7.5 g of compound No. 19 as identified in Table 1. over a period of 30 minutes under cooling with ice pyridine was distilled off under reduced pressure The residual oily substance was dissolved in 100 ml of toluene washed sequentially with water Then, toluene was distilled off The residue was purified by silica gel column chromatography a solvent mixture of ethyl acetate/n-hexane=1/3 as the developer

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

Procedure: 6.5 g of 4-(2,3-dihydro-2,2-dimethyl-5-benzofuranyloxy)aniline was dissolved in 30 ml of pyridine, and 3.8 g of N-methoxy-N-methylcarbamoyl chloride was gradually dropwise added thereto over a period of 30 minutes under cooling with ice. Stirring was continued for 1.5 hours, and then pyridine was distilled off under reduced pressure. The residual oily substance was dissolved in 100 ml of toluene, and washed sequentially with water, a dilute hydrochloric acid aqueous solution and a saturated sodium chloride aqueous solution. Then, toluene was distilled off. The residue was purified by silica gel column chromatography by using a solvent mixture of ethyl acetate/n-hexane=1/3 as the developer, to obtain 7.5 g of compound No. 19 as identified in Table 1. over a period of 30 minutes under cooling with ice pyridine was distilled off under reduced pressure The residual oily substance was dissolved in 100 ml of toluene washed sequentially with water Then, toluene was distilled off The residue was purified by silica gel column chromatography a solvent mixture of ethyl acetate/n-hexane=1/3 as the developer

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

Procedure: A mixture of 1-methyl-1H-1,2,4-triazole (3.15 mL, 55.56 mmol) and methoxy(methyl)carbamic chloride (7.55 g, 61.11 mmol) in acetonitrile (60 mL) was cooled in an ice water bath before addition of TEA (8.52 mL, 61.11 mmol). The mixture was allowed to slowly warm to room temperature and was then stirred overnight. The material was diluted with ether and solids were filtered and rinsed well with ether. The filtrate was concentrated and the residue was taken up in ether. Insoluble solids were filtered off and rinsed well with additional ether. The filtrate was concentrated to give and oil that was chromatographed on silica gel (100% CH2Cl2 followed by gradient elution to 40% EtOAc in CH2Cl2) to afford product as an oil that slowly solidified. 6.13 g (65% yield). were filtered rinsed well with ether The filtrate was concentrated Insoluble solids were filtered off rinsed well with additional ether The filtrate was concentrated to give oil that was chromatographed on silica gel (100% CH2Cl2 followed by gradient elution to 40% EtOAc in CH2Cl2) to afford product as an oil that

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

Procedure: A mixture of 1-methyl-1H-1,2,4-triazole (3.15 mL, 55.56 mmol) and methoxy(methyl)carbamic chloride (7.55 g, 61.11 mmol) in acetonitrile (60 mL) was cooled in an ice water bath before addition of TEA (8.52 mL, 61.11 mmol). The mixture was allowed to slowly warm to room temperature and was then stirred overnight. The material was diluted with ether and solids were filtered and rinsed well with ether. The filtrate was concentrated and the residue was taken up in ether. Insoluble solids were filtered off and rinsed well with additional ether. The filtrate was concentrated to give and oil that was chromatographed on silica gel (100% CH2Cl2 followed by gradient elution to 40% EtOAc in CH2Cl2) to afford product as an oil that slowly solidified. 6.13 g (65% yield). were filtered rinsed well with ether The filtrate was concentrated Insoluble solids were filtered off rinsed well with additional ether The filtrate was concentrated to give oil that was chromatographed on silica gel (100% CH2Cl2 followed by gradient elution to 40% EtOAc in CH2Cl2) to afford product as an oil that