Methyl chloroformate → Dimethyl 2-(3-fluoro-4-(trifluoromethyl)benzyl)piperidine-1,4-dicarboxylate

HRID 1963333Notes

Reaction equation

HRID 1963333 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[C:19]([F:22])([F:21])[F:20])[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:32](Cl)(=[O:35])[O:33][CH3:34]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[C:19]([F:22])([F:20])[F:21])[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:32]([O:33][CH3:34])=[O:35]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 66731785HCID 66731785, compound

Product 1

HCID 66734842Dimethyl 2-(3-fluoro-4-(trifluoromethyl)benzyl)piperidine-1,4-dicarboxylateYield 102%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 2-(3-fluoro-4-(trifluoromethyl)benzyl)piperidine-4-carboxylate (5.96 g, 18.67 mmol) in DCM (100 mL) cooled in an ice-bath was added DIPEA (4 mL, 22.96 mmol) followed by methyl carbonochloridate (1.617 mL, 20.53 mmol). After completed addition the reaction mixture was stirred at room temperature for 2 h. The solvents were evaporated and the residue partitioned between ethyl acetate and 3.8 M HCl. After phase separation the organic layer was washed with brine, then dried over MgSO4 and evaporated. Dimethyl 2-(3-fluoro-4-(trifluoromethyl)benzyl)piperidine-1,4-dicarboxylate (7.17 g, 102%) was isolated as a pale yellow oil.

Workup

  1. additionaddition the reaction mixture
  2. customThe solvents were evaporated
  3. customthe residue partitioned between ethyl acetate and 3.8 M HCl
  4. customAfter phase separation the organic layer
  5. washwas washed with brine
  6. dry with materialdried over MgSO4
  7. customevaporated

Sources & evidence

ORD record
ord-56d0a9aa2e2d4c2d9dcaffd88a0813a5
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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