N-methoxy-N-methylbutanamide

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:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a dry 3-necked flask under argon at -50° C., n-butyl lithium (0.0025 M, 0.021 ml) was added to 150 ml diethylether. Then 4.16 grams 3-bromoquinoline in 2 ml THF was added dropwise while stirring and maintaining the temperature at -60° C. to -55° C. The solution was stirred for 30 minutes, and 2.3 grams N-methyl-N-methoxybutanamide were then added dropwise at -50° C. and the solution was stirred an additional 30 minutes The solution was then allowed to warm to 0° C. and stirred for one hour. The reaction was quenched with a saturated solution of ammonium chloride and the THF layer separated, washed with brine, separated, and dried over magnesium sulfate. Filtration through diatomaceous earth, followed by concentration and subsequent thin layer chromatography (35% ethylacetate/65% CH2Cl2) gave a total yield of 2.03 g (51%) of the title compound. maintaining the temperature at -60° C. to -55° C The solution was stirred for 30 minutes the solution was stirred an additional 30 minutes The solution stirred for one hour The reaction was quenched with a saturated solution of ammonium chloride the THF layer separated washed with brine separated dried over magnesium sulfate Filtration through diatomaceous earth followed by concentration and subsequent thin layer chromatography (35% ethylacetate/65% CH2Cl2)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a dry 3-necked flask under argon at -50° C., n-butyl lithium (0.0025 M, 0.021 ml) was added to 150 ml diethylether. Then 4.16 grams 3-bromoquinoline in 2 ml THF was added dropwise while stirring and maintaining the temperature at -60° C. to -55° C. The solution was stirred for 30 minutes, and 2.3 grams N-methyl-N-methoxybutyramide were then added dropwise at -50° C. and the solution was stirred an additional 30 minutes. The solution was then allowed to warm to 0° C. and stirred for one hour. The reaction was quenched with a saturated solution of ammonium chloride and the THF layer separated, washed with brine, separated, and dried over magnesium sulfate. Filtration through diatomaceous earth, followed by concentration and subsequent thin layer chromatography (35% ethylacetate/65% CH2Cl2) gave a total yield of 2.03 g (51%) of the title compound. maintaining the temperature at -60° C. to -55° C The solution was stirred for 30 minutes the solution was stirred an additional 30 minutes stirred for one hour The reaction was quenched with a saturated solution of ammonium chloride the THF layer separated washed with brine separated dried over magnesium sulfate Filtration through diatomaceous earth followed by concentration and subsequent thin layer chromatography (35% ethylacetate/65% CH2Cl2)

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

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a dry 3-necked flask under argon at -50° C., n-butyl lithium (0.0025 M, 0.021 ml) was added to 150 ml diethylether. Then 4.16 grams 3-bromoquinoline in 2 ml THF was added dropwise while stirring and maintaining the temperature at -60° C. to -55° C. The solution was stirred for 30 minutes, and 2.3 grams N-methyl-N-methoxybutanamide were then added dropwise at -50° C. and the solution was stirred an additional 30 minutes. The solution was then allowed to warm to 0° C. and stirred for one hour. The reaction was quenched with a saturated solution of ammonium chloride and the THF layer separated, washed with brine, separated, and dried over magnesium sulfate. Filtration through diatomaceous earth, followed by concentration and subsequent thin layer chromatography (35% ethylacetate/65% CH2Cl2) gave a total yield of 2.03 g (51%) of the title compound. maintaining the temperature at -60° C. to -55° C The solution was stirred for 30 minutes the solution was stirred an additional 30 minutes stirred for one hour The reaction was quenched with a saturated solution of ammonium chloride the THF layer separated washed with brine separated dried over magnesium sulfate Filtration through diatomaceous earth followed by concentration and subsequent thin layer chromatography (35% ethylacetate/65% CH2Cl2)

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 50 mL (65 mmol) of 1.3M sec-butyl lithium in cyclohexane was added slowly to N-tert-butoxycarbonyl-3-methoxy-2-methylaniline (7.7 g, 32.5 mmol) in 100 mL of THF keeping the temperature below -40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to -10° C. and then the bath replaced. After the temperature had cooled to -60° C., 4.3 g (32.5 mmol) of N-methoxy-N-methylbutanamide in an equal volume of THF was added dropwise. The reaction mixture was stirred 1 hour, the cooling bath removed and stirred an additional 22 hours. It was then poured into a mixture of 200 mL of ether and 200 mL of 0.5N HCl. The organic layer was separated, washed with brine, dried over MgSO4, and concentrated at reduced pressure to give 9.9 g of crude 1-[2-(tert-butoxycarbonylamino)-6-methoxyphenyl]-2-pentanone. This material was dissolved in 100 mL of methylene chloride and 20 mL of trifluoroacetic acid and stirred for a total of 23 hours. The mixture was washed with water, dried (MgSO4) and concentrated at reduced pressure. The residue was chromatographed on silica gel eluting with 20% EtOAc/hexane to give 2.19 g of 4-methoxy-2-propyl-1H-indole as an oil. The bath was removed to rise to -10° C. the cooling bath removed stirred an additional 22 hours It was then poured into a mixture of 200 mL of ether and 200 mL of 0.5N HCl The organic layer was separated washed with brine dried over MgSO4 concentrated at reduced pressure