Benzyl chloroformate → 1-(Phenylmethyl) (3R)-1,3-piperidinedicarboxylate

HRID 1020059Notes

Reaction equation

HRID 1020059 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([OH:9])=[O:8])[CH2:2]1.C(=O)(O)[O-].[Na+].Cl[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]>C1COCC1.O>[CH2:19]([O:18][C:16]([N:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([OH:9])=[O:8])[CH2:2]1)=[O:17])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 1796510(-)-Nipecotic acid

Product 1

HCID 7365381-(Phenylmethyl) (3R)-1,3-piperidinedicarboxylateYield 36%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (R)-piperidine-3-carboxylic acid (XXVII) (5.0 g, 39 mmol) in a mixture of 50 ml of THF and 20 ml of water was cooled to 0° C. and sodium bicarbonate (6.5 g, 77.4 mmol) and benzyl chloroformate (8.0 g, 46.4 mmol) were added simultaneously. The reaction mixture was stirred at 0° C. for 30 min and at room temperature for 3 hours and concentrated under reduced pressure. The remaining aqueous phase was extracted with ethyl ether to remove excess of benzyl chloroformate, then it was acidified with 1 M HCl solution to pH 6 followed by extraction with ethyl acetate. The organic layer was separated, dried over sodium sulfate and evaporated to provide (R)-piperidine-1,3-dicarboxylic acid 1-benzyl ester (XXVIII) (3.7 g, 36%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionThe remaining aqueous phase was extracted with ethyl ether
  3. customto remove excess of benzyl chloroformate
  4. extractionfollowed by extraction with ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. customevaporated

Sources & evidence

ORD record
ord-35ed7565ed0f4c14948f8dd1f09fdc2a
Source dataset
uspto-grants-2014_05
Patent number
US08716296B2

Reaction notes

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