Methyl chloroformate → Dimethyl 2-(3,5-difluorobenzyl)piperidine-1,4-dicarboxylate

HRID 1963319Notes

Reaction equation

HRID 1963319 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([F:19])[CH:18]=1)[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]=[C:17]([F:19])[CH:18]=1)[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 chloroformate2×HCID 81531DiisopropylethylamineHCID 66731630Methyl 2-(3,5-difluorobenzyl)piperidine-4-carboxylate

Product 1

HCID 66734958Dimethyl 2-(3,5-difluorobenzyl)piperidine-1,4-dicarboxylateYield 99.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 2-(3,5-difluorobenzyl)piperidine-4-carboxylate (7.082 g, 26.30 mmol) was dissolved in DCM (170 mL) and DIPEA (5.50 mL, 31.56 mmol), then methyl carbonochloridate (2.88 mL, 36.58 mmol) was added. The reaction mixture was stirred at room temperature for 3 h, then additional methyl carbonochloridate (0.7 mL, 8.89 mmol) was added. The solution was stirred for 30 min then washed with 0.1 M HCl and satd NaHCO3. The organic phase was dried and concentrated to give dimethyl 2-(3,5-difluorobenzyl)piperidine-1,4-dicarboxylate (8.55 g, 99%). MS m/z 328 (M+H)+

Workup

  1. stirringThe solution was stirred for 30 min
  2. washthen washed with 0.1 M HCl
  3. customThe organic phase was dried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-611e5d7d47c54d4c9cd864a83a2e034e
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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