Triethylamine → HCID 66731611, compound

HRID 1963256Notes

Reaction equation

HRID 1963256 reaction equation
[F:1][C:2]1([F:23])[CH2:7][CH2:6][CH:5]([CH2:8][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])[CH2:4][CH2:3]1.[Br-].[Li+].CCN(CC)CC.CC(OC)(C)C>C(#N)C.O>[F:23][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([CH2:8][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])[CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734830HCID 66734830, compound

Product 1

HCID 66731611HCID 66731611, compoundYield 88.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Dimethyl 2-((4,4-difluorocyclohexyl)methyl)piperidine-1,4-dicarboxylate (5.7 g, 17.10 mmol) was dissolved in acetonitrile (75 mL) and water (1.5 mL), then lithium bromide (11.88 g, 136.78 mmol) was added. Et3N (9.53 mL, 68.39 mmol) was added to the solution. The resulting yellow suspension was heated at reflux for 2 h. Water (100 mL) and MTBE (300 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 to yield 2-((4,4-difluorocyclohexyl)methyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (4.82 g, 88%) as a white solid.

Workup

  1. temperatureThe resulting yellow suspension was heated
  2. temperatureat reflux for 2 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-d88a7542226a44cab3e6d20b89610275
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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