Methyl chloroformate → Dimethyl 2-(3,4-difluorobenzyl)piperidine-1,4-dicarboxylate

HRID 1963307Notes

Reaction equation

HRID 1963307 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][CH:6]1[CH2:11][CH:10]([C:12]([O:14][CH3:15])=[O:13])[CH2:9][CH2:8][NH:7]1.CCN(C(C)C)C(C)C.[C:29](Cl)(=[O:32])[O:30][CH3:31]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][CH:6]1[CH2:11][CH:10]([C:12]([O:14][CH3:15])=[O:13])[CH2:9][CH2:8][N:7]1[C:29]([O:30][CH3:31])=[O:32]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 66731879Methyl 2-(3,4-difluorobenzyl)piperidine-4-carboxylate

Product 1

HCID 66734915Dimethyl 2-(3,4-difluorobenzyl)piperidine-1,4-dicarboxylateYield 71.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 2-(3,4-difluorobenzyl)piperidine-4-carboxylate (8.115 g, 30.14 mmol) was dissolved in DCM (200 mL) and DIPEA (6.30 mL, 36.16 mmol), then methyl carbonochloridate (3.3 mL, 41.91 mmol) was added. The solution was stirred at room temperature for 2 h. The reaction mixture was washed with 0.1 M HCl satd NaHCO3. The organic phase was passed through a phase separator and evaporated. The residue was redissolved in ether/pentane, 80/20, the solution washed with 1 M HCl 5 times, then with satd NaHCO3 and brine, dried over MgSO4, filtered and evaporated to yield dimethyl 2-(3,4-difluorobenzyl)piperidine-1,4-dicarboxylate (7.05 g, 71%). MS m/z 328 (M+H)+

Workup

  1. washThe reaction mixture was washed with 0.1 M HCl
  2. customevaporated
  3. dissolutionThe residue was redissolved in ether/pentane
  4. wash80/20, the solution washed with 1 M HCl 5 times
  5. dry with materialwith satd NaHCO3 and brine, dried over MgSO4
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-17d9f395475a4969a20873a1d1170d17
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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