Methyl chloroformate → Dimethyl 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)-piperidine-1,4-dicarboxylate

HRID 1963213Notes

Reaction equation

HRID 1963213 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:14]2[CH2:19][CH:18]([C:20]([O:22][CH3:23])=[O:21])[CH2:17][CH2:16][NH:15]2)[CH:6]=[C:7]([F:13])[C:8]=1[C:9]([F:12])([F:11])[F:10].CCN(C(C)C)C(C)C.[C:33](Cl)(=[O:36])[O:34][CH3:35]>C(Cl)Cl>[F:13][C:7]1[CH:6]=[C:5]([CH:14]2[CH2:19][CH:18]([C:20]([O:22][CH3:23])=[O:21])[CH2:17][CH2:16][N:15]2[C:33]([O:34][CH3:35])=[O:36])[CH:4]=[C:3]([F:2])[C:8]=1[C:9]([F:12])([F:10])[F:11]

Participants

5

Reactant 3

HCID 6586Methyl chloroformate2×HCID 81531DiisopropylethylamineHCID 86646600Methyl 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)piperidine-4-carboxylate hydrochloride

Product 1

HCID 66732303Dimethyl 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)-piperidine-1,4-dicarboxylateYield 86.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Methyl 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)piperidine-4-carboxylate hydrochloride (3.118 g, 8.67 mmol) and DIPEA (3.02 mL, 17.34 mmol) were dissolved in DCM (30 mL). Methyl carbonochloridate (1.024 mL, 13.00 mmol) was added and the reaction stirred at room temperature for 1.5 h. Additional methyl carbonochloridate (0.341 mL, 4.33 mmol) was added and stirring continued for 0.5 h. DCM (170 mL) was added. The organic phase was washed with 0.1 M HCl (2×200 mL), satd NaHCO3 (200 mL), dried with a phase separator and evaporated in vacuo to yield dimethyl 2-(3,5-difluoro-4-(trifluoromethyl)phenyl)-piperidine-1,4-dicarboxylate (2.85 g, 86%) as a colorless oil. MS m/z 382 (M+H)+

Workup

  1. stirringstirring
  2. waitcontinued for 0.5 h
  3. washThe organic phase was washed with 0.1 M HCl (2×200 mL), satd NaHCO3 (200 mL)
  4. customdried with a phase separator
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-1c1bcb9cea864b1695afcd8a1eca6aa0
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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