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

HRID 1963131Notes

Reaction equation

HRID 1963131 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:10]2[CH2:15][CH:14]([C:16]([O:18][CH3:19])=[O:17])[CH2:13][CH2:12][NH:11]2)[CH:6]=[CH:7][C:8]=1[F:9].CCN(C(C)C)C(C)C.Cl[C:30]([O:32][CH3:33])=[O:31]>C(Cl)Cl>[F:2][C:3]1[CH:4]=[C:5]([CH:10]2[CH2:15][CH:14]([C:16]([O:18][CH3:19])=[O:17])[CH2:13][CH2:12][N:11]2[C:30]([O:32][CH3:33])=[O:31])[CH:6]=[CH:7][C:8]=1[F:9]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 66732136Methyl 2-(3,4-difluorophenyl)piperidine-4-carboxylate hydrochloride

Product 1

HCID 66734537Dimethyl 2-(3,4-difluorophenyl)piperidine-1,4-dicarboxylateYield 100.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Methyl 2-(3,4-difluorophenyl)piperidine-4-carboxylate hydrochloride (6.1 g, 20.91 mmol) and DIPEA (9.13 mL, 52.28 mmol) were dissolved in DCM (30 mL). Methyl chloroformate (1.944 mL, 25.09 mmol) was added and the reaction stirred at room temperature for 1.5 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 yielding dimethyl 2-(3,4-difluorophenyl)piperidine-1,4-dicarboxylate (6.58 g, 100%) as a dark oil. MS m/z 314 (M+H)+.

Workup

  1. washThe organic phase was washed with 0.1 M HCl (2×200 mL), satd NaHCO3 (200 mL)
  2. customdried with a phase separator
  3. customevaporated in vacuo

Sources & evidence

ORD record
ord-788e79ce75c64aa7af7d23444cea651a
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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