Methyl chloroformate → Methyl 4-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)piperazine-1-carboxylate

HRID 1618748Notes

Reaction equation

FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([F:20])=[CH:16][C:17]=2[F:19])[N:12]=[C:11]([N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[C:10]=1[CH3:27].C(=O)([O-])[O-].[K+].[K+].Cl[C:35]([O:37][CH3:38])=[O:36]>CC(C)=O>[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([F:20])=[CH:16][C:17]=2[F:19])[N:12]=[C:11]([N:21]2[CH2:26][CH2:25][N:24]([C:35]([O:37][CH3:38])=[O:36])[CH2:23][CH2:22]2)[C:10]=1[CH3:27]

Participants

Conditions

Temperature: 80 °C

Procedure

The 4-chloro-5,7-difluoro-3-methyl-2-(piperazin-1-yl)quinoline 2,2,2-trifluoroacetate (150 mg, 0.37 mmol), potassium carbonate (360 mg, 2.60 mmol) and methyl chloroformate (0.11 mL, 1.50 mmol) were added to acetone (3.0 mL). The slurry was heated in a microwave reactor at 80° C. for 3 h. The reaction mixture was concentrated and the residue was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (1×30 mL) and dried over MgSO4 to give methyl 4-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)piperazine-1-carboxylate. Mass Spectrum (ESI) m/e=356.2 (M+1).

Workup

concentrationThe reaction mixture was concentrated
customthe residue was partitioned between water and EtOAc
extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
washThe combined organic layers were washed with brine (1×30 mL)
dry with materialdried over MgSO4

Sources & evidence

ORD record: ord-39ea38c5dfc44709abdbaede3f0de25a
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

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