Citric Acid → rel-1-(1,1-Dimethylethyl) 3-methyl (3R,5S)-1,3,5-piperidinetricarboxylate

HRID 1475179Notes

Reaction equation

HRID 1475179 reaction equation
C1([C@H](N)C)C=CC=CC=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([C:23]([O:25][CH3:26])=[O:24])[CH2:20][C@H:19]([C:27]([OH:29])=[O:28])[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].CO.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O>[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([C:23]([O:25][CH3:26])=[O:24])[CH2:20][C@H:19]([C:27]([OH:29])=[O:28])[CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 887MethanolHCID 86680826(3S,5R)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid (1R)-1-phenylethylamine salt

Product 1

HCID 11358159rel-1-(1,1-Dimethylethyl) 3-methyl (3R,5S)-1,3,5-piperidinetricarboxylateYield 96.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

(3S,5R)-1-(tert-Butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid (1R)-1-phenylethylamine salt (20.0 g, 49.0 mmol), methanol (20 mL) and water (80 mL) were charged. A solution of citric acid (11.3 g, 58.8 mmol) in water (20.0 mL) was added dropwise at 20-30° C., and the mixture was stirred at the same temperature for 1.5 hr. The precipitated crystals were collected by filtration, washed with water (60 mL), and dried under reduced pressure at 50° C. to give (3S,5R)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid as a white crystalline powder (13.5 g, yield 96.1%).

Workup

  1. filtrationThe precipitated crystals were collected by filtration
  2. washwashed with water (60 mL)
  3. customdried under reduced pressure at 50° C.

Sources & evidence

ORD record
ord-f52f1c3a6adf4c6bb12d934e2913e97c
Source dataset
uspto-grants-2015_04
Patent number
US09018374B2

Reaction notes

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