Reaction #3457

Reaction equation

sec-butyl lithium

N-tert-butoxycarbonyl-3-methoxy-2-methylaniline

N-methoxy-N-methylpropanamide

→

1-[2-(tert-butoxycarbonylamino)-6-methoxyphenyl]-2-butanone

Solvents

cyclohexane

THF

THF

Conditions

Workup

1. 1
   OtherThe bath was removed
2. 2
   Otherto rise to 0° C.
3. 3
   Otherthe cooling bath removed
4. 4
   workup.STIRRINGstirred an additional 18 hours
5. 5
   workup.ADDITIONIt was then poured into a mixture of 300 mL of ether and 400 mL of 0.5N HCl
6. 6
   OtherThe organic layer was separated
7. 7
   Washwashed with water, brine
8. 8
   Dryingdried over MgSO4
9. 9
   Concentrationconcentrated at reduced pressure

Procedure

A solution of 140 mL (0.18 mol) of 1.3M sec-butyl lithium in cyclohexane was added slowly to N-tert-butoxycarbonyl-3-methoxy-2-methylaniline (21.3 g, 0.09 mol) in 250 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 0° C. and then the bath replaced. After the temperature had cooled to -60° C., 18.5 g (0.18 mol) of N-methoxy-N-methylpropanamide in an equal volume of THF was added dropwise. The reaction mixture was stirred 5 minutes, the cooling bath removed and stirred an additional 18 hours. It was then poured into a mixture of 300 mL of ether and 400 mL of 0.5N HCl. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated at reduced pressure to give 25.5 g of a crude of 1-[2-(tert-butoxycarbonylamino)-6-methoxyphenyl]-2-butanone. This material was dissolved in 250 mL of methylene chloride and 50 mL of trifluoroacetic acid and stirred for a total of 17 hours. The mixture was concentrated at reduced pressure and ethyl acetate and water added to the remaining oil. The ethyl acetate was separated, washed with brine, dried (MgSO4) and concentrated. The residue was chromatographed three times on silica eluting with 20% EtOAc/hexane to give 13.9 g of 2-ethyl-4-methoxy-1H-indole.

Source