Triethylamine → HCID 66731960, compound

HRID 1963329Notes

Reaction equation

HRID 1963329 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[CH2:5][CH:6]1[CH2:11][CH:10]([C:12]([O:14]C)=[O:13])[CH2:9][CH2:8][N:7]1[C:16]([O:18][CH3:19])=[O:17].[Br-].[Li+].C(N(CC)CC)C>C(#N)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([C:23]([F:26])([F:24])[F:25])[CH:22]=1)[CH2:5][CH:6]1[CH2:11][CH:10]([C:12]([OH:14])=[O:13])[CH2:9][CH2:8][N:7]1[C:16]([O:18][CH3:19])=[O:17]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 82050Lithium BromideHCID 66734710HCID 66734710, compound

Product 1

HCID 66731960HCID 66731960, compoundYield 96.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of dimethyl 2-(3-fluoro-5-(trifluoromethyl)benzyl)piperidine-1,4-dicarboxylate (4.94 g, 13.09 mmol) in acetonitrile (60 mL) and water (1.2 mL) was added lithium bromide (9.10 g, 104.74 mmol) and triethylamine (7.26 mL, 52.37 mmol). The resulting mixture was heated under reflux for 2 h, then cooled to room temperature. Water was added and acetonitrile removed by evaporation. The aqueous layer was further diluted with water, then washed with MTBE. The organic layer was extracted with water. The combined aqueous layers were acidified with 3.8 M HCl, a colorless precipitate formed. The aqueous layer was extracted with DCM three times. The combined organic layers were dried over MgSO4 and evaporated. 2-(3-Fluoro-5-(trifluoromethyl)benzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (4.58 g, 96%) was isolated as a pale yellow viscous oil. MS m/z 364 (M+H)+

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for 2 h
  3. customacetonitrile removed by evaporation
  4. additionThe aqueous layer was further diluted with water
  5. washwashed with MTBE
  6. extractionThe organic layer was extracted with water
  7. customa colorless precipitate formed
  8. extractionThe aqueous layer was extracted with DCM three times
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. customevaporated

Sources & evidence

ORD record
ord-2096f0ad8b964d7ea5375d480b8663e3
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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