Isobutylene → 2-(2,5-Dichloro-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester

HRID 2047695Notes

Reaction equation

HRID 2047695 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][CH:5]=1.[Cl:12][C:13]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:14]=1[CH:15]=O.[CH2:22]=[C:23]([CH3:25])[CH3:24].FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>CC#N.O>[CH3:1][O:2][C:3]([C:4]1[CH:5]=[C:6]2[C:7](=[CH:8][CH:9]=1)[NH:10][CH:15]([C:14]1[CH:17]=[C:18]([Cl:21])[CH:19]=[CH:20][C:13]=1[Cl:12])[CH2:22][C:23]2([CH3:25])[CH3:24])=[O:11]

Participants

7

Reactant 4

HCID 8255IsobutyleneHCID 12082Methyl 4-aminobenzoateHCID 807022,5-DichlorobenzaldehydeHCID 2733225Ytterbium triflate

Product 1

HCID 665875772-(2,5-Dichloro-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 4-aminobenzoic acid methyl ester (1.5 g, 10 mmol) and 2,5-dichloro-benzaldehyde (1.8 g, 10 mmol) in MeCN (5 mL) were added isobutene (2.1 mL, 30 mmol) and ytterbium(III) trifluoromethanesulfonate (Yb(OTf)3) (1.3 g, 2 mmol). The resulting mixture was stirred at 80° C. for 18 hours in sealed tube. The mixture was diluted with water (50 mL), extracted with diethyl ether (50 mL×3). The extracts were washed with water (100 mL) and brine (100 mL) and then dried over anhydrous Na2SO4. The solvent was removed in vacuo and the residue was purified by ISCO combi-flash chromatography (gradient elution, 0-10% ethyl acetate in petroleum ether) to 2-(2,5-dichloro-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (1.8 g, 50%) as a light yellow solid (reference: Kiselyov, A. S. et al., Tetrahedron 54 (1998) 5089): MS (ESI+) [(M+H)+] 364.2.

Workup

  1. extractionextracted with diethyl ether (50 mL×3)
  2. washThe extracts were washed with water (100 mL) and brine (100 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by ISCO combi-flash chromatography (gradient elution, 0-10% ethyl acetate in petroleum ether) to 2-(2,5-dichloro-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (1.8 g, 50%) as a light yellow solid (reference

Sources & evidence

ORD record
ord-4099d39dbc0845c8bc6a6712b46184b8
Source dataset
uspto-grants-2013_11
Patent number
US08592594B2

Reaction notes

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