Methyl chloroformate → Dimethyl 2-(4-chloro-2-fluorophenyl)piperidine-1,4-dicarboxylate

HRID 1963175Notes

Reaction equation

HRID 1963175 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH:12]([C:14]([O:16][CH3:17])=[O:15])[CH2:11][CH2:10][NH:9]2)=[C:4]([F:18])[CH:3]=1.CCN(C(C)C)C(C)C.[C:28](Cl)(=[O:31])[O:29][CH3:30]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH:12]([C:14]([O:16][CH3:17])=[O:15])[CH2:11][CH2:10][N:9]2[C:28]([O:29][CH3:30])=[O:31])=[C:4]([F:18])[CH:3]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 66732030Methyl 2-(4-chloro-2-fluorophenyl)piperidine-4-carboxylate

Product 1

HCID 66734801Dimethyl 2-(4-chloro-2-fluorophenyl)piperidine-1,4-dicarboxylateYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 2-(4-chloro-2-fluorophenyl)piperidine-4-carboxylate (7.45 g, 27.42 mmol) was dissolved into DCM (120 mL) then DIPEA (11.97 mL, 68.55 mmol) was added. Methyl carbonochloridate (3.02 mL, 38.39 mmol) was added dropwise to the solution. The mixture was stirred at room temperature for 3 h. The mixture was washed with 0.1 M HCl (2×100 mL) and satd NaHCO3 (100 mL), then dried through a phase-separator and evaporated leaving dimethyl 2-(4-chloro-2-fluorophenyl)piperidine-1,4-dicarboxylate (7.77 g, 86%) as an orange oil. MS m/z 330 (M+H)+

Workup

  1. washThe mixture was washed with 0.1 M HCl (2×100 mL) and satd NaHCO3 (100 mL)
  2. customdried through a phase-separator
  3. customevaporated

Sources & evidence

ORD record
ord-7f64395cd86c47628f4d4fc74ffd8a09
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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