Triethylamine → HCID 66731982, compound

HRID 1963164Notes

Reaction equation

HRID 1963164 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[N:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH:13]([C:15]([O:17]C)=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])=[CH:5][CH:4]=1.[Br-].[Li+].CCN(CC)CC.CC(OC)(C)C>C(#N)C.O>[CH3:22][O:21][C:19]([N:10]1[CH2:11][CH2:12][CH:13]([C:15]([OH:17])=[O:16])[CH2:14][CH:9]1[C:6]1[CH:7]=[N:8][C:3]([C:2]([F:23])([F:1])[F:24])=[CH:4][CH:5]=1)=[O:20]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734495HCID 66734495, compound

Product 1

HCID 66731982HCID 66731982, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Crude dimethyl 2-(6-(trifluoromethyl)pyridin-3-yl)piperidine-1,4-dicarboxylate (2.9 g, 8.38 mmol) was dissolved in acetonitrile (35 mL) and water (0.700 mL), then lithium bromide (2.91 g, 33.50 mmol) was added. Et3N (2.334 mL, 16.75 mmol) was added and the resulting yellow suspension was heated under reflux for 1 h. Water (100 mL) and MTBE (150 mL) were added. The phases were separated and the organic layer was extracted with water (2 times). The pooled water layers were acidified to pH 1 with 3.8 M HCl and extracted into MTBE (2 times). The combined organic layer was dried over Na2SO4, filtered and evaporated yielding crude 1-(methoxycarbonyl)-2-(6-(trifluoromethyl)pyridin-3-yl)piperidine-4-carboxylic acid (2.5 g, 90%) as a slightly yellow solid. MS m/z 333 (M+H)+

Workup

  1. temperaturethe resulting yellow suspension was heated
  2. temperatureunder reflux for 1 h
  3. customThe phases were separated
  4. extractionthe organic layer was extracted with water (2 times)
  5. extractionextracted into MTBE (2 times)
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-c3b29d9ad37b4a44a616d4a55f38d035
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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