Dimethylformamide → 4-Methoxy-3-(4-methoxy-butyl)-benzaldehyde

HRID 1158447Notes

Reaction equation

HRID 1158447 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([CH2:10][CH2:11][CH2:12][CH2:13][O:14][CH3:15])[CH:3]=1.C([Li])CCC.CCCCCC.CN([CH:30]=[O:31])C>C1COCC1>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([CH:30]=[O:31])=[CH:3][C:4]=1[CH2:10][CH2:11][CH2:12][CH2:13][O:14][CH3:15]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8058HexaneHCID 214586274-Bromo-1-methoxy-2-(4-methoxybutyl)benzeneHCID 178418339Butyllithium

Product 1

HCID 862481464-Methoxy-3-(4-methoxy-butyl)-benzaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-bromo-1-methoxy-2-(4-methoxy-butyl)-benzene (8.10 g, 29.7 mmol; described in EP0678 503 B1) in absolute THF (170 mL), cooled to −78° C., is added dropwise over 30 min and under an argon atmosphere a 1.6M solution of n-butyllithium in hexane (20.4 mL, 32.6 mmol). After stirring for 5 min, a mixture of DMF (5.03 mL, 65.2 mmol) in THF (20 mL) is added over 30 min at −78° C. Stirring is continued over 15 min at −78° C., and the reaction mixture is gradually warmed and stirred for an additional hour at room temperature before quenching with 1N HCl. The aqueous layer is extracted with diethyl ether (3×200 mL), the combined organics are dried (Na2SO4) and concentrated. Purification by flash chromatography on silica gel (hexane/AcOEt 4:1) gives the title compound as yellowish oil. TLC, Rf (hexane/AcOEt 4:1)=0.27. MS: 223.2 [M+H]+. 1H-NMR (CDCl3): δ 1.6-1.74 (m, 4H) 2.70 (t, 2H), 3.37 (s, 3H), 3.43 (t, 2H), 3.96 (s, 3H), 6.99 (dd, 1H), 7.73 (d, 1H), 7.76 (dd, 1H), 9.70 (s, 1H) ppm.

Workup

  1. additionis added over 30 min at −78° C
  2. stirringStirring
  3. waitis continued over 15 min at −78° C.
  4. temperaturethe reaction mixture is gradually warmed
  5. stirringstirred for an additional hour at room temperature
  6. custombefore quenching with 1N HCl
  7. extractionThe aqueous layer is extracted with diethyl ether (3×200 mL)
  8. dry with materialthe combined organics are dried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification by flash chromatography on silica gel (hexane/AcOEt 4:1)

Sources & evidence

ORD record
ord-9c9a82d1a3ac45abb53562a5bfc84a12
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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