Triethylamine → HCID 66731660, compound

HRID 1963207Notes

Reaction equation

HRID 1963207 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([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:4][C:3]=1[F:23].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH:9]2[CH2:14][CH:13]([C:15]([OH:17])=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])=[CH:4][C:3]=1[F:23]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734743HCID 66734743, compound

Product 1

HCID 66731660HCID 66731660, compoundYield 91.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-(4-chloro-3,5-difluorophenyl)piperidine-1,4-dicarboxylate (1.83 g, 5.26 mmol) was dissolved in acetonitrile (30 mL) and water (0.600 mL), then lithium bromide (3.66 g, 42.10 mmol) was added. Triethylamine (2.92 mL, 21.05 mmol) was added and the resulting suspension was heated under reflux for 4 h. MTBE (100 mL) and water (50 mL) were added, the phases separated and the organic layer was extracted with water. The combined aqueous layers were acidified to pH 1 with 3.8 M HCl and extracted with MTBE. The combined organic layers were dried over Na2SO4 and evaporated to yield 2-(4-chloro-3,5-difluoro-phenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (1.600 g, 91%) as a light yellow solid. MS m/z 332 (M−H)−

Workup

  1. temperaturethe resulting suspension was heated
  2. temperatureunder reflux for 4 h
  3. customthe phases separated
  4. extractionthe organic layer was extracted with water
  5. extractionextracted with MTBE
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-445f5e561cbe40b2a0c9b4a1a41fdac5
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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