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Triethylamine → 2-(2-Fluoro-4-(trifluoromethyl)phenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963222
Notes
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Reaction equation

HRID 1963222 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH:16]([C:18]([O:20]C)=[O:19])[CH2:15][CH2:14][N:13]1[C:22]([O:24][CH3:25])=[O:23].[Br-].[Li+].CCN(CC)CC.CC(OC)(C)C>C(#N)C.O>[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:9])[F:11])[CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH:16]([C:18]([OH:20])=[O:19])[CH2:15][CH2:14][N:13]1[C:22]([O:24][CH3:25])=[O:23]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66735134Dimethyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)piperidine-1,4-dicarboxylate

Product 1

HCID 667315582-(2-Fluoro-4-(trifluoromethyl)phenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidYield 94.1%

Reagents, catalysts & solvents

2
HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)piperidine-1,4-dicarboxylate (5.33 g, 14.67 mmol) was dissolved in acetonitrile (35 mL) and water (0.700 mL), then lithium bromide (10.19 g, 117.37 mmol) was added. Et3N (8.18 mL, 58.68 mmol) was added and the resulting yellow suspension was heated under reflux for 1 h. Water (50 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 with MTBE (2 times). The combined organic layer was dried over Na2SO4, filtered and evaporated yielding 2-(2-fluoro-4-(trifluoromethyl)phenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (4.82 g, 94%) as a slightly yellow solid. MS m/z 348 (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 with MTBE (2 times)
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-27d29b41274142fa90ad2593346f530e
Source dataset
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08415378B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes