Hydrochloric Acid → 1-(1,1-Dimethylethyl) (3R)-1,3-piperidinedicarboxylate

HRID 479799Notes

Reaction equation

HRID 479799 reaction equation
[C:1]([N:8]1[CH2:18][CH2:17][CH2:16][C@@H:10]([C:11]([O:13]CC)=[O:12])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Li+].[OH-].Cl>CO.O>[C:1]([N:8]1[CH2:18][CH2:17][CH2:16][C@@H:10]([C:11]([OH:13])=[O:12])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 15144461-tert-Butyl 3-ethyl (3R)-piperidine-1,3-dicarboxylate

Product 1

HCID 6435161-(1,1-Dimethylethyl) (3R)-1,3-piperidinedicarboxylateYield 92.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
4 °C

Procedure

To a solution of ethyl N-Boc-(R)-nipecotate (7.61 g, 29.6 mmol) in 25 mL of methanol was added LiOH (2.48 g, 2 eq.) in 25 mL of H2O dropwise at 4° C. The reaction mixture was stirred overnight at 4° C. The pH of the mixture was adjusted to ca. 1 by adding aqueous HCl (10% w/w). The aqueous layer was extracted with ethyl acetate (3×100 mL). The extracts were combined and washed with aqueous NH4Cl (sat., 2×50 mL), brine (50 mL), and dried over anhydrous Na2SO4, filtered and evaporated to give N-Boc-(R)-nipecotic acid 25 as a white solid 6.25 g (92%).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
  2. washwashed with aqueous NH4Cl (sat., 2×50 mL), brine (50 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-dbc7558724754427bfcc48beef2f0952
Source dataset
uspto-grants-2003_11
Patent number
US06645980B1

Reaction notes

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