Acetonitrile → HCID 66732454, compound

HRID 1963176Notes

Reaction equation

HRID 1963176 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH:12]([C:14]([O:16]C)=[O:15])[CH2:11][CH2:10][N:9]2[C:18]([O:20][CH3:21])=[O:19])=[C:4]([F:22])[CH:3]=1.C(#N)C.[Br-].[Li+].CCN(CC)CC>CC(OC)(C)C.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH:12]([C:14]([OH:16])=[O:15])[CH2:11][CH2:10][N:9]2[C:18]([O:20][CH3:21])=[O:19])=[C:4]([F:22])[CH:3]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 82050Lithium BromideHCID 66734801Dimethyl 2-(4-chloro-2-fluorophenyl)piperidine-1,4-dicarboxylate

Product 1

HCID 66732454HCID 66732454, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

Dimethyl 2-(4-chloro-2-fluorophenyl)piperidine-1,4-dicarboxylate (7.77 g, 23.56 mmol) was dissolved into acetonitrile (100 mL) and water (2.000 mL), then lithium bromide (16.37 g, 188.51 mmol) was added. Et3N (13.14 mL, 94.25 mmol) was added and the resulting yellow suspension was heated under reflux for 2 h. Water (200 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 MgSO4, filtered and evaporated yielding 2-(4-chloro-2-fluorophenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (7.28 g, 98%) as a yellow semi-solid. MS m/z 316 (M+H)+

Workup

  1. temperaturethe resulting yellow suspension was heated
  2. temperatureunder 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 MgSO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-618b900a8c8d43908cbf42274890805a
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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