Cesium carbonate → HCID 66559506, compound

HRID 1750134Notes

Reaction equation

HRID 1750134 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:20]1[CH:21]=[C:22]([CH:38]=[CH:39][CH:40]=1)[CH2:23][N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=2[Cl:37])[CH2:26][CH2:25]1.CC(C(CC(C(C)(C)C)=O)=O)(C)C>CN1C(=O)CCC1.Cl[Cu]>[Cl:37][C:31]1[C:32]([Cl:36])=[CH:33][CH:34]=[CH:35][C:30]=1[N:27]1[CH2:26][CH2:25][N:24]([CH2:23][C:22]2[CH:21]=[C:20]([CH:40]=[CH:39][CH:38]=2)[O:1][C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][C:8](=[O:12])[NH:9]3)=[CH:4][CH:3]=2)[CH2:29][CH2:28]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 27857587-Hydroxy-3,4-dihydrocarbostyrilHCID 66559508HCID 66559508, compound

Product 1

HCID 66559506HCID 66559506, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 7-hydroxy-3,4-dihydroquinolin-2(1H)-one (196 mg, 1.2 mmol in NMP was added Cs2CO3 (391 mg, 1.2 mmol). The slurry was degassed by evacuating and filling the reaction flask with N2 three times. Intermediate 53 (240 mg, 0.6 mmol) and TMHD (11 mg, 0.06 mmol) were added followed by the addition of CuCl (60 mg, 0.6 mmol). The reaction mixture was degassed by evacuating and filling the reaction flask with N2 three times, and then warmed to 120° C. under N2 for 7.5 h. The reaction mixture was cooled to rt and diluted with Et2O. The slurry was filtered and the filtercake was washed with Et2O. Combined filtrates were washed with 2 N HCl, 0.6 N HCl, 2 M NaOH, and 10% aq NaCl. The resulting organic layer was dried, concentrated, and purified by flash chromatography on a silica gel column (elution with PE/EtOAc=1:1) to give 7-(3-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)phenoxy)-3,4-dihydro quinolin-2(1H)-one (compound 30) (110 mg, 38%). 1H NMR (300 MHz, CDCl3): δ 7.62 (s, 1H), 7.31 (d, J=7.2 Hz, 2H), 7.15-7.05 (m, 4H), 6.96-6.89 (m, 2H), 6.62 (dd, J=2.1 Hz, 8.1 Hz, 1H), 6.41 (d, J=2.1 Hz, 1H), 3.57 (s, 2H), 3.06 (m, 4H), 2.94 (t, J=7.5 Hz, 2H), 2.66-2.61 (m, 5H). HPLC: 99%, RT 2.637 min. MS (ESI) m/z 482.1 [M+H]+. mp: 182-183° C.

Workup

  1. customThe slurry was degassed
  2. customby evacuating
  3. customThe reaction mixture was degassed
  4. customby evacuating
  5. temperatureThe reaction mixture was cooled to rt
  6. additiondiluted with Et2O
  7. filtrationThe slurry was filtered
  8. washthe filtercake was washed with Et2O
  9. washCombined filtrates were washed with 2 N HCl, 0.6 N HCl, 2 M NaOH, and 10% aq NaCl
  10. customThe resulting organic layer was dried
  11. concentrationconcentrated
  12. custompurified by flash chromatography on a silica gel column (elution with PE/EtOAc=1:1)

Sources & evidence

ORD record
ord-82f9fafdeea04df193d2341faabd2c23
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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