N-tert-butoxycarbonyl-3-methoxy-2-methylaniline → 1-[2-(Tert-butoxycarbonylamino)-6-methoxyphenyl]-2-butanone

HRID 1368992Notes

Reaction equation

HRID 1368992 reaction equation
C([Li])(CC)C.[C:6]([O:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[C:15]=1[CH3:22])=[O:12])([CH3:9])([CH3:8])[CH3:7].CON(C)[C:26](=[O:29])[CH2:27][CH3:28]>C1CCCCC1.C1COCC1>[C:6]([O:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[C:15]=1[CH2:22][C:26](=[O:29])[CH2:27][CH3:28])=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

6

Reactant 3

HCID 10609918N-tert-butoxycarbonyl-3-methoxy-2-methylanilineHCID 11344007N-Methoxy-N-methylpropionamideHCID 178418400CID 53628100

Product 1

HCID 107324851-[2-(Tert-butoxycarbonylamino)-6-methoxyphenyl]-2-butanone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-60 °C

Procedure

A solution of 140 mL (0.18 mol) of 1.3M sec-butyl lithium in cyclohexane is 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 is removed and the temperature allowed to rise to 0° C. and then the bath replaced. After the temperature has cooled to −60° C., 18.5 g (0.18 mmol) of N-methoxy-N-methylpropanamide in an equal volume of THF iss added dropwise. The reaction mixture is stirred 5 minutes, the cooling bath removed and stirred an additional 18 hours. It is then poured into a mixture of 300 mL of ether and 400 mL of 0.5N HCl. The organic layer is separated, washing 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 is dissolved in 250 mL of methylene chloride and 50 mL of trifluoroacetic acid and stirred for a total of 17 hours. The mixture is concentrated at reduced pressure and ethyl acetate and water added to the remaining oil. The ethyl acetate is separated, washed with brine, dried (MgSO4) and concentrated. The residue is chromatographed three times on silica eluting with 20% EtOAc/hexane to give 13.9 g of 2-ethyl-4-methoxy-1H-indole.

Workup

  1. customThe bath is removed
  2. customto rise to 0° C.
  3. additionadded dropwise
  4. customthe cooling bath removed
  5. stirringstirred an additional 18 hours
  6. additionIt is then poured into a mixture of 300 mL of ether and 400 mL of 0.5N HCl
  7. customThe organic layer is separated
  8. washwashing with water, brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated at reduced pressure

Sources & evidence

ORD record
ord-ff65968312c24d71bb5652130b30ca49
Source dataset
uspto-grants-2003_06
Patent number
US06576654B1

Reaction notes

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