Lithium Hydroxide → 1-(1,1-Dimethylethyl) (3R)-1,3-piperidinedicarboxylate

HRID 218359Notes

Reaction equation

HRID 218359 reaction equation
[N:1]1([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([O:9]CC)=[O:8])[CH2:2]1.[Li+].[OH-]>CO.O>[C:15]([O:14][C:12]([N:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([OH:9])=[O:8])[CH2:2]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 2

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

Product 1

HCID 6435161-(1,1-Dimethylethyl) (3R)-1,3-piperidinedicarboxylateYield 92%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of (R)-1-tert-butyl 3-ethyl piperidine-1,3-dicarboxylate (2.2 kg, 8.469 mol, 1 eq) in 5 L of MeOH was added a solution of LiOH (629.6 g, 15 mol, 1.77 eq) in 7.5 L of water at 0-5° C. After addition, the mixture was stirred overnight at room temperature. TLC showed the starting material was consumed. The pH of the system was adjusted to 7 by addition of saturated citric acid solution. Most of the methanol was removed. The pH was adjusted to 4-5 with citric acid. The mixture was extracted 3 times with 5 L of CH2Cl2, the organic layers were combined and dried over Na2SO4 and evaporated to afford a white solid (1.775 kg, 92%).

Workup

  1. additionAfter addition
  2. customwas consumed
  3. additionThe pH of the system was adjusted to 7 by addition of saturated citric acid solution
  4. customMost of the methanol was removed
  5. extractionThe mixture was extracted 3 times with 5 L of CH2Cl2
  6. dry with materialdried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-c0cc896433f041678ca2a0347224deaf
Source dataset
uspto-grants-2012_06
Patent number
US08198453B2

Reaction notes

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