Carbon Dioxide → (+/-)-N-[4-(Dimethylamino)benzyl]-N-(4-isopropylphenyl)-2-methoxy-5,6,7,8-tetrahydroquinoline-8-carboxamide

HRID 33771

Reaction equation

HRID 33771 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[N:4]=1.[Li][C:14]([CH3:17])([CH3:16])[CH3:15].[C:18](=[O:20])=O.[CH3:21]N(C=O)C.CN(C)C1C=CC(C[NH:33][C:34]2[CH:39]=[CH:38][C:37]([CH:40]([CH3:42])[CH3:41])=[CH:36][CH:35]=2)=CC=1.[CH3:46][N:47]1[CH2:52]CO[CH2:49][CH2:48]1.CCCP(O)(O)=O.C([O-])(O)=O.[Na+].CCOC(C)=O>CCOCC>[CH3:52][N:47]([CH3:46])[C:48]1[CH:21]=[CH:17][C:14]([CH2:16][N:33]([C:34]2[CH:35]=[CH:36][C:37]([CH:40]([CH3:41])[CH3:42])=[CH:38][CH:39]=2)[C:18]([CH:6]2[C:5]3[N:4]=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][C:10]=3[CH2:9][CH2:8][CH2:7]2)=[O:20])=[CH:15][CH:49]=1

Participants

10

Reactant 8

HCID 280Carbon DioxideHCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 204484Propylphosphonic acidHCID 181802832-Methoxy-5,6,7,8-tetrahydroquinolineHCID 21957887N-(4-(Dimethylamino)benzyl)-4-isopropylbenzenamineHCID 86584982Sodium bicarbonate ethyl acetateHCID 178418306HCID 178418306, compound

Product 1

HCID 11576159(+/-)-N-[4-(Dimethylamino)benzyl]-N-(4-isopropylphenyl)-2-methoxy-5,6,7,8-tetrahydroquinoline-8-carboxamide

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a 0.22 M solution of 2-methoxy-5,6,7,8-tetrahydroquinoline in Et2O at −78° C. was added 1.7 equiv of t-BuLi [1,7M] over 5 min. After allowing the reaction to warm up to 0° C. and stirring at this temperature for 30 min, a stream of CO2(g) was then allowed to flow into the flask. The final mixture was allowed to warm to room temperature and the solvent was removed by the flow of CO2. To a solution/suspension of the resulting crude lithium carboxylate salt in DMF (12 equiv) at 0° C. was successively added 1.2 equiv of N-[4-(dimethylamino)benzyl]4-isopropylaniline, 12 equiv of 4-methylmorpholine and 4.0 equiv of 1-propylphosphonic acid cyclic anhydride (50% in EtOAc). After allowing the reaction to warm to room temperature overnight, this mixture was poured into a separatory funnel containing aqueous NaHCO3/EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The crude material was further purified by flash chromatography, eluting with a gradient from 100% hexanes to 25% EtOAc/hexanes to provide the title compound as a white solid.

Workup

  1. customthe reaction
  2. temperatureto warm to room temperature
  3. customthe solvent was removed by the flow of CO2
  4. customthe reaction
  5. temperatureto warm to room temperature overnight
  6. additionthis mixture was poured into a separatory funnel
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was further purified by flash chromatography
  12. washeluting with a gradient from 100% hexanes to 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-ea7852a2269f4205a78fa8db6484b238
Source dataset
uspto-grants-2008_09
Patent number
US07429666B2

Linked notes

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