Methanol → Benzyl 4-formylpiperidine-1-carboxylate

HRID 2387931Notes

Reaction equation

HRID 2387931 reaction equation
C[C:2]1([C:18]([O-])=[O:19])[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:4][CH2:3]1.CC(C[AlH]CC(C)C)C.CO.[Cl-].[Na+]>C1(C)C=CC=CC=1>[CH:18]([CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:9])[CH2:4][CH2:3]1)=[O:19]

Participants

6

Reactant 4

HCID 887MethanolHCID 5234Sodium ChlorideHCID 14487Diisobutylaluminum hydride2×HCID 86188531HCID 86188531, compound

Product 1

HCID 2776272Benzyl 4-formylpiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 1-benzyl 4-methylpiperidine-1,4-dicarboxylate (10 g) in toluene (100 ml) under nitrogen was cooled to −78° C. DIBAL-H (60.9 ml) was then added dropwise at −78° C., and the mixture was stirred for one hour at that temperature (TLC monitoring). Because the reaction was incomplete, a further 0.2 eq. of DIBAL-H were added and stirring was carried out for a further 30 minutes (TLC monitoring: some starting material and the corresponding alcohol were detectable). Methanol (40 ml) followed by saturated sodium chloride solution (40 ml) were added slowly to the reaction mixture at −78° C. The mixture was filtered over Celite and the solvent was removed in vacuo. The residue was extracted with ethyl acetate (3×75 ml), dried (Na2SO4) and concentrated in vacuo. The crude product so obtained was purified by column chromatography (silica gel, 20% ethyl acetate/hexane). Yield: 4.3 g (49%)

Workup

  1. stirringstirring
  2. waitwas carried out for a further 30 minutes
  3. additionwere added slowly to the reaction mixture at −78° C
  4. filtrationThe mixture was filtered over Celite
  5. customthe solvent was removed in vacuo
  6. extractionThe residue was extracted with ethyl acetate (3×75 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f1ac1b2c83a842b7862a2f05947de0e4
Source dataset
uspto-grants-2012_09
Patent number
US08269000B2

Reaction notes

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