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Cesium carbonate → 1,1-Dimethylethyl 4-(6-fluoro-2-methyl-5-quinolinyl)-1-piperazinecarboxylate

HRID 734547
Notes
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Reaction equation

HRID 734547 reaction equation
Br[C:2]1[C:11]([F:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:13])=[N:7]2.[N:14]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C1(P(C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=C(C3C4C(=CC=CC=4)C=CC=3)C3C(C=2)=CC=CC=3)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[F:12][C:11]1[C:2]([N:17]2[CH2:16][CH2:15][N:14]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18]2)=[C:3]2[C:8](=[CH:9][CH:10]=1)[N:7]=[C:6]([CH3:13])[CH:5]=[CH:4]2
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 130353135-Bromo-6-fluoro-2-methylquinolineHCID 18630801Bis(diphenylphosphino)-1,1'-binaphthyl

Product 1

HCID 574443131,1-Dimethylethyl 4-(6-fluoro-2-methyl-5-quinolinyl)-1-piperazinecarboxylateYield 65.8%

Reagents, catalysts & solvents

1
HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5-bromo-6-fluoro-2-methylquinoline (Chem. Pharm. Bull., 1989, 37(8), 2103-8, 0.285 g), 1,1-dimethylethyl 1-piperazinecarboxylate (0.265 g, 1.2 equiv.), Pd(OA)2 (15 mol %, 0.04 g), bis(diphenylphosphino)-1,1′-binaphthyl (BINAP, 30 mol %, 0.221 g), cesium carbonate (1.5 equiv. 0.580 g) and toluene (3.5 mL) were stirred at 120° C. for 20 h in a sealed tube. The mixture was cooled to room temperature and partitioned between ethyl acetate and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. This crude product was purified by flash chromatography [SiO2; DCM-MeOH (99:1)→(90:10)] to afford the title compound as colourless solid (0.270 g, 65% yield).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate and brine
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThis crude product was purified by flash chromatography [SiO2; DCM-MeOH (99:1)→(90:10)]

Sources & evidence

ORD record
ord-15aa0ca294aa46838da57cc671299141
Source dataset
uspto-grants-2009_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07592346B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes