Methanol → Benzyl 4-formylpiperidine-1-carboxylate

HRID 453908Notes

Reaction equation

HRID 453908 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. Then DIBAL-H (60.9 ml) was added dropwise at −78° C., and the mixture was stirred for 1 h at that temperature (TLC monitoring). Because the reaction was incomplete, a further 0.2 eq. of DIBAL-H was added and stirring was carried out for a further 30 min (TLC monitoring: some starting material and the corresponding alcohol were detectable). Methanol (40 ml) followed by sat. 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 under vacuum. The residue was extracted with ethyl acetate (3×75 ml), dried (Na2SO4) and concentrated under vacuum. 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 min
  3. additionwere added slowly to the reaction mixture at −78° C
  4. filtrationThe mixture was filtered over celite
  5. customthe solvent was removed under vacuum
  6. extractionThe residue was extracted with ethyl acetate (3×75 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-45d598a0f01d49a68f90abaa3bc8556f
Source dataset
uspto-grants-2013_07
Patent number
US08492559B2

Reaction notes

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