1-Piperidinecarboxaldehyde → 5-Chloro-2-methylbenzaldehyde

HRID 1066362Notes

Reaction equation

HRID 1066362 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH3:9].[Li]CCCC.[CH:15](N1CCCCC1)=[O:16]>C1COCC1>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]([CH3:9])=[C:2]([CH:7]=1)[CH:15]=[O:16]

Participants

5

Reactant 3

HCID 174291-PiperidinecarboxaldehydeHCID 6098982-Bromo-4-chloro-1-methylbenzeneHCID 178418339Butyllithium

Product 1

HCID 123475655-Chloro-2-methylbenzaldehydeYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 2-bromo-4-chloro toluene (20.0 g; 97.3 mmol) in 300 mL of THF at −78° C. was added n-BuLi 2.5M (40.8 mL) dropwise. After 20 min. 1-formylpiperidine (11.4 mL; 103.0 mmol) in 10 mL of THF was added dropwise. After 30 min the reaction mixture was brought to 0° C. and quenched with HCl (10%) and diluted with EtOAc. The organic phase was collected, dry and the solvent evaporated to yield 13.3 g (89%) of 5-chloro-2-methylbenzaldehyde. This crude aldehyde was mixed with 1.1 equivalent of triethyl phosphonoacetate in THF. Sodium hydride 80% (1.3 equivalent ) was added portionwise and 1 h later the reaction was quenched with 25% NH4Cl. The reaction mixture was diluted with EtOAc and the organic phase collected, dried and the solvent removed. The crude oil was purified on a short pad of silica gel using 5% EtOAc in hexane to afford 16.67 g of the title compound.

Workup

  1. waitAfter 30 min the reaction mixture was brought to 0° C.
  2. customquenched with HCl (10%)
  3. additiondiluted with EtOAc
  4. customThe organic phase was collected
  5. customdry
  6. customthe solvent evaporated

Sources & evidence

ORD record
ord-685f033296a143ab800395405b272e7d
Source dataset
uspto-grants-2001_06
Patent number
US06242493B1

Reaction notes

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