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

HRID 581147Notes

Reaction equation

HRID 581147 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:30])[CH2:27][CH2:28][CH3:29]>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:30])[CH2:27][CH2:28][CH3:29])=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

6

Reactant 3

HCID 10609918N-tert-butoxycarbonyl-3-methoxy-2-methylanilineHCID 13704543N-Methoxy-N-methylbutyramideHCID 178418400CID 53628100

Product 1

HCID 107335371-[2-(Tert-butoxycarbonylamino)-6-methoxyphenyl]-2-pentanoneYield 99.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-60 °C

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.

Workup

  1. customThe bath was removed
  2. customto rise to -10° C.
  3. customthe cooling bath removed
  4. stirringstirred an additional 22 hours
  5. additionIt was then poured into a mixture of 200 mL of ether and 200 mL of 0.5N HCl
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated at reduced pressure

Sources & evidence

ORD record
ord-9f7adf97d09f4ee8a1b03351c0c24fb5
Source dataset
uspto-grants-1999_07
Patent number
US05919810

Reaction notes

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