Hydrochloric Acid → Dimethyl 2-(2,4-difluorobenzyl)piperidine-1,4-dicarboxylate

HRID 1963323Notes

Reaction equation

HRID 1963323 reaction equation
[F:1][C:2]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:3]=1[CH2:4][CH:5]1[CH2:10][CH:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][CH2:7][NH:6]1.CCN(C(C)C)C(C)C.[C:29](Cl)(=[O:32])[O:30][CH3:31].Cl>C(Cl)Cl.CC(OC)(C)C>[F:1][C:2]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:3]=1[CH2:4][CH:5]1[CH2:10][CH:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][CH2:7][N:6]1[C:29]([O:30][CH3:31])=[O:32]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 66731679Methyl 2-(2,4-difluorobenzyl)piperidine-4-carboxylate

Product 1

HCID 66734674Dimethyl 2-(2,4-difluorobenzyl)piperidine-1,4-dicarboxylateYield 99%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of methyl 2-(2,4-difluorobenzyl)piperidine-4-carboxylate (7.1 g, 26.37 mmol) in DCM (100 mL) was added DIPEA (6.5 mL, 37.32 mmol) followed by methyl carbonochloridate (2.3 mL, 29.21 mmol) dropwise. After completed addition the reaction mixture was stirred at room temperature for 4 h, then 2 M HCl was added. The organic layer was diluted with MTBE, the biphasic mixture was filtered to remove insolubles and after phase separation the organic layer was washed with brine and satd NaHCO3, dried over MgSO4 and evaporated to give dimethyl 2-(2,4-difluorobenzyl)piperidine-1,4-dicarboxylate (8.51 g, 99%) as a dark oil. MS m/z 328 (M+H)+

Workup

  1. additionaddition the reaction mixture
  2. filtrationthe biphasic mixture was filtered
  3. customto remove insolubles
  4. customafter phase separation the organic layer
  5. washwas washed with brine and satd NaHCO3
  6. dry with materialdried over MgSO4
  7. customevaporated

Sources & evidence

ORD record
ord-f25ef08408944987a4ee940cd622431c
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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