Triethylamine → HCID 66732104, compound

HRID 1963312Notes

Reaction equation

HRID 1963312 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:3]=1[CH2:4][CH:5]1[CH2:10][CH:9]([C:11]([O:13]C)=[O:12])[CH2:8][CH2:7][N:6]1[C:15]([O:17][CH3:18])=[O:16].[Br-].[Li+].C(N(CC)CC)C.CC(OC)(C)C>C(#N)C.O>[F:1][C:2]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:3]=1[CH2:4][CH:5]1[CH2:10][CH:9]([C:11]([OH:13])=[O:12])[CH2:8][CH2:7][N:6]1[C:15]([O:17][CH3:18])=[O:16]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734456Dimethyl 2-(2,5-difluorobenzyl)piperidine-1,4-dicarboxylate

Product 1

HCID 66732104HCID 66732104, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of dimethyl 2-(2,5-difluorobenzyl)piperidine-1,4-dicarboxylate (8.08 g, 24.69 mmol) in acetonitrile (85 mL) and water (1.7 mL) was added lithium bromide (4.95 mL, 197.48 mmol) and triethylamine (13.69 mL, 98.74 mmol). The reaction mixture was heated to reflux for 2.5 h, then allowed to cool to room temperature. Water (150 mL) and MTBE (300 mL) was added. The aqueous phase was separated and the organic phase was extracted twice with water. The water phases were combined and 4.0 M HCl was added until a pH of 1 was obtained. The aqueous was extracted with MTBE (300 mL×2). The organic phases were combined, washed with brine, dried with Na2SO4 and evaporated under reduced pressure to give 2-(2,5-difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (7.4 g, 96%). MS m/z 314 (M+H)+

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2.5 h
  3. customThe aqueous phase was separated
  4. extractionthe organic phase was extracted twice with water
  5. addition4.0 M HCl was added until a pH of 1
  6. customwas obtained
  7. extractionThe aqueous was extracted with MTBE (300 mL×2)
  8. washwashed with brine
  9. dry with materialdried with Na2SO4
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-646a8fb5c1cb4d8da110a5b14e4f6acc
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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