Citric Acid → tert-butyl (2R)-2-formylpiperidine-1-carboxylate

HRID 2243875Notes

Reaction equation

HRID 2243875 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=O.CC(C[AlH]CC(C)C)C.CO.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1>[C:14]([O:13][C:11]([N:6]1[CH2:7][CH2:8][CH2:9][CH2:10][C@@H:5]1[CH:3]=[O:2])=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 887MethanolHCID 14487Diisobutylaluminum hydrideHCID 450724561-tert-Butyl 2-methyl (2R)-piperidine-1,2-dicarboxylate

Product 1

HCID 10703805tert-butyl (2R)-2-formylpiperidine-1-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To the title compound of Example 1.1 (5.4 g, 22.1 mmol) in toluene (50 mL) at −78° C. was added 1.5 M DIBAL in toluene (33.8 mL, 50.7 mmol) drop-wise over 40 minutes. Methanol (120 mL) was then added drop-wise at −78° C. over 10 minutes. The reaction mixture was moved to an ice-bath where 10% wt citric acid (500 mL) was added and then mixture was stirred for an additional 1 hour. After the resulting mixture was extracted with ethyl acetate (2 times), the organic layer washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title product as a colorless oil (3.0 g, 64%).

Workup

  1. customThe reaction mixture was moved to an ice-bath
  2. extractionAfter the resulting mixture was extracted with ethyl acetate (2 times)
  3. washthe organic layer washed with water and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-51819c6fbbb648eaa72275fbab77728c
Source dataset
uspto-grants-2010_03
Patent number
US07678796B2

Reaction notes

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