Diisopropylamine → 3-Bromo-6-fluoro-2-methoxybenzaldehyde

HRID 1983519Notes

Reaction equation

HRID 1983519 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=1[O:21][CH3:22].[CH:23](N1CCCCC1)=[O:24]>CCCCCC.O1CCCC1.O.C(O)(=O)C>[Br:13][C:14]1[C:15]([O:21][CH3:22])=[C:16]([C:17]([F:20])=[CH:18][CH:19]=1)[CH:23]=[O:24]

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 174291-PiperidinecarboxaldehydeHCID 70180432-Bromo-5-fluoroanisoleHCID 178418339Butyllithium

Product 1

HCID 222610733-Bromo-6-fluoro-2-methoxybenzaldehyde

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

In an atmosphere of nitrogen gas, 18.7 ml of a 2.66 M solution of n-butyllithium in hexane was added to a solution of 5 g of N,N-diisopropylamine in 89 ml tetrahydrofuran at −78° C. After stirring at the same temperature for 1 hour and 10 minutes, 9.27 g of 1-bromo-4-fluoro-2-methoxy-benzene obtained in Production Example II-1-a was added dropwise. After stirring at the same temperature for 1.5 hours, 5.52 ml of N-formylpiperidine was added dropwise. After stirring at the same temperature for 25 minutes, 9 ml of acetic acid was added at the same temperature, water was added at room temperature, and the mixture was extracted with diethyl ether for three times. The extract was sequentially washed with 0.2 N hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The crude product was purified and separated by silica gel column chromatography, to give 5.65 g of the title compound as pale yellow crystals.

Workup

  1. additionwas added dropwise
  2. stirringAfter stirring at the same temperature for 1.5 hours
  3. stirringAfter stirring at the same temperature for 25 minutes
  4. additionwas added at room temperature
  5. extractionthe mixture was extracted with diethyl ether for three times
  6. washThe extract was sequentially washed with 0.2 N hydrochloric acid, water and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated
  9. customThe crude product was purified
  10. customseparated by silica gel column chromatography

Sources & evidence

ORD record
ord-d9e4f57550b248ec9dfdf99fd19e69e1
Source dataset
uspto-grants-2009_06
Patent number
US07541376B2

Reaction notes

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