1-Piperidinecarboxaldehyde → HCID 59130008, compound

HRID 1992241Notes

Reaction equation

HRID 1992241 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][CH2:11][CH3:12])=[C:4]([F:13])[C:3]=1[O:14]COCCOC.C([Li])CCC.[CH:26](N1CCCCC1)=[O:27]>C1COCC1.CCCCCC>[F:13][C:4]1[C:3]([OH:14])=[C:2]([CH:7]=[CH:6][C:5]=1[O:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH:26]=[O:27]

Participants

6

Reactant 3

HCID 174291-PiperidinecarboxaldehydeHCID 59653567HCID 59653567, compoundHCID 178418339Butyllithium

Product 1

HCID 59130008HCID 59130008, compoundYield 69.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

21.0 g (59.3 mmol) of 1-bromo-4-butoxy-3-fluoro-2-(2-methoxyethoxymethoxy)benzene (9) are dissolved in 200 ml of THF and treated at −78° C. with 37 ml (60 mmol) of a 15% strength solution of n-butyllithium in hexane. After 1 h, 6.8 ml (61 mmol) of N-formylpiperidine are added dropwise in 50 mmol of THF. The mixture is subsequently stirred for 1 h, and the mixture is allowed to thaw. After hydrolysis, the solution is acidified and extracted with MTBE. The combined organic phases are washed with water and dried over sodium sulfate. The solvent is removed in vacuo, the residue is taken up in 150 ml of THF, and after addition of 30 ml of conc. hydrochloric acid the mixture is stirred at room temperature overnight. The mixture is taken up in MTBE and washed with water (pH 5). The solvent is removed in vacuo and the crude product is filtered through silica gel using MTBE. 8.80 g (53%, 2 stages) of 3-fluoro-4-butoxy-2-hydroxybenzaldehyde (11) are obtained as a slightly violet solid.

Workup

  1. customAfter hydrolysis
  2. extractionextracted with MTBE
  3. washThe combined organic phases are washed with water
  4. dry with materialdried over sodium sulfate
  5. customThe solvent is removed in vacuo
  6. additionafter addition of 30 ml of conc. hydrochloric acid the mixture
  7. stirringis stirred at room temperature overnight
  8. washwashed with water (pH 5)
  9. customThe solvent is removed in vacuo
  10. filtrationthe crude product is filtered through silica gel

Sources & evidence

ORD record
ord-971901ab3f394ae8a7642d3f629748df
Source dataset
uspto-grants-2010_01
Patent number
US07648742B2

Reaction notes

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