Hydrochloric Acid → Dimethyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)piperidine-1,4-dicarboxylate

HRID 1963194Notes

Reaction equation

HRID 1963194 reaction equation
Cl.[F:2][C:3]1[CH:8]=[C:7]([O:9][C:10]([F:13])([F:12])[F:11])[CH:6]=[CH:5][C:4]=1[CH:14]1[CH2:19][CH:18]([C:20]([O:22][CH3:23])=[O:21])[CH2:17][CH2:16][NH:15]1.CCN(C(C)C)C(C)C.[C:33](Cl)(=[O:36])[O:34][CH3:35].Cl>ClCCl>[F:2][C:3]1[CH:8]=[C:7]([O:9][C:10]([F:13])([F:12])[F:11])[CH:6]=[CH:5][C:4]=1[CH:14]1[CH2:19][CH:18]([C:20]([O:22][CH3:23])=[O:21])[CH2:17][CH2:16][N:15]1[C:33]([O:34][CH3:35])=[O:36]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 66732336Methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)piperidine-4-carboxylate hydrochloride

Product 1

HCID 66734961Dimethyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)piperidine-1,4-dicarboxylateYield 102.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)piperidine-4-carboxylate hydrochloride (4.97 g, 13.89 mmol) was dissolved in dichloromethane (50 mL) and DIPEA (6.05 mL, 34.73 mmol). Methyl carbonochloridate (1.313 mL, 16.67 mmol) was added and the reaction mixture was stirred at room temperature for 4 h. 0.1 M HCl was added and the aqueous layer extracted with DCM. The combined organic layers were filtered through a phase separator and evaporated. Crude dimethyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)piperidine-1,4-dicarboxylate (5.39 g, 102%) was obtained as a yellow oil. MS m/z 380 (M+H)+

Workup

  1. extractionthe aqueous layer extracted with DCM
  2. filtrationThe combined organic layers were filtered through a phase separator
  3. customevaporated

Sources & evidence

ORD record
ord-9d9171385a9d469980c0e7cfde5c3f15
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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