Veratrole → N-Boc-(2,3-dimethoxyphenyl)-4-piperidinylmethanone

HRID 51272Notes

Reaction equation

HRID 51272 reaction equation
[C:1]1([O:9][CH3:10])[C:2](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O:3][CH3:4].C([Li])CCC.COCN[C:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21]>O1CCCC1.CCCCCC>[CH3:4][O:3][C:2]1[C:1]([O:9][CH3:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21]

Participants

6

Reactant 3

HCID 7043VeratroleHCID 442032024-(Methoxymethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 46780868N-Boc-(2,3-dimethoxyphenyl)-4-piperidinylmethanone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of veratrole (16.6 g, 0.120 mol) in tetrahydrofuran (130 mL) at −78° C. was added n-butyllithium (50.5 mL, of a 2.5 M solution in hexane, 0.126 mmol). The resulting mixture was allowed to warm to ambient temperature over 1 hour and then stirred at this temperature for 4 hours before recooling to −78° C. and treating the resulting slurry with a solution of 4-[(methoxymethylamino)carbonyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (15) (30.71 g, 0.1128 mol) in tetrahydrofuran (180 mL). The reaction mixture was allowed to warm slowly to ambient temperature overnight and then recooled to 0° C. and quenched by the addition of saturated aqueous ammonium chloride solution (110 mL). The aqueous layer was extracted with ether (110 mL) and the combined organic extracts were washed with brine (220 mL), dried (MgSO4) and concentrated in vacuum to give the title compound (7).

Workup

  1. custombefore recooling to −78° C.
  2. temperatureto warm slowly to ambient temperature overnight
  3. customrecooled to 0° C.
  4. customquenched by the addition of saturated aqueous ammonium chloride solution (110 mL)
  5. extractionThe aqueous layer was extracted with ether (110 mL)
  6. washthe combined organic extracts were washed with brine (220 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-bdaddbe533fe4de9940652eb33532718
Source dataset
uspto-grants-2004_03
Patent number
US06713627B2

Reaction notes

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