Dimethylformamide → tert-butyl (2R,6S)-2-formyl-6-methylpiperidine-1-carboxylate

HRID 1937132Notes

Reaction equation

HRID 1937132 reaction equation
[C:1]([O:5][C:6]([N:8]1CCC[CH2:10][C@@H:9]1[CH3:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)CCN(C)C.[CH:23]([Li])([CH2:25][CH3:26])[CH3:24].CN(C)C=[O:31].[Cl-].[NH4+]>C(OCC)C>[CH:24]([C@H:23]1[CH2:25][CH2:26][CH2:10][C@H:9]([CH3:14])[N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[O:31]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 11019870(S)-(+)-N-(Boc)-2-methylpiperidineHCID 178418400CID 53628100

Product 1

HCID 10878893tert-butyl (2R,6S)-2-formyl-6-methylpiperidine-1-carboxylateYield 55%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-20 °C

Procedure

To 2.50 g(12.5 mmol) of (S)-N-tert-butoxycarbonyl-2-methylpiperidine in 25 ml of dehydrated diethyl ether solution were added 1.89 ml(1 equivalent) of N,N,N′,N′-tetramethylethylenediamine at −60° C. under an atmosphere of argon, and then 13.3 ml(1.1 equivalent) of sec-butyllithium were added dropwise. After the temperature of reaction mixture was raised to −20° C., it was cooled again to −70° C. and 1.46 ml(1.5 equivalents) of N,N-dimethylformamide were added dropwise. After stirring for about 2 hours, 20 ml of saturated solution of ammonium chloride were added to the reaction mixture to stop the reaction. The aqueous layer was separated, which was extracted with ether(10 ml×3). Combined organic layers were dried over anhydrous magnesium sulfate, filtered and solvent was distilled off. The residue was purified by means of silica gel column chromatography(hexane:ethyl acetate=8:1) to obtain 1.58 g of (2R,6S)-tert-butyl 2-formyl-6-methyl-1-piperidinecarboxylate (yield 55%).

Workup

  1. customAfter the temperature of reaction mixture
  2. temperatureit was cooled again to −70° C.
  3. customthe reaction
  4. customThe aqueous layer was separated
  5. extractionwhich was extracted with ether(10 ml×3)
  6. dry with materialCombined organic layers were dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. distillationsolvent was distilled off
  9. customThe residue was purified by means of silica gel column chromatography(hexane:ethyl acetate=8:1)

Sources & evidence

ORD record
ord-559936f0eb38414598db990101c6ed96
Source dataset
uspto-grants-2002_05
Patent number
US06392059B1

Reaction notes

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