Sodium Bicarbonate → methyl 4-((2S,4R)-1-acetyl-4-((isopropoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

HRID 2366895Notes

Reaction equation

HRID 2366895 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)O1.[CH3:20][CH:21]([O:23][C:24](=[O:41])[NH:25][C@H:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33](Br)[CH:34]=2)[N:29]([C:37](=[O:39])[CH3:38])[C@@H:28]([CH3:40])[CH2:27]1)[CH3:22].C([O-])(O)=O.[Na+]>C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.C(Cl)Cl.O1CCOCC1>[C:37]([N:29]1[C:30]2[C:35](=[CH:34][C:33]([C:9]3[CH:10]=[CH:11][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:17][CH:18]=3)=[CH:32][CH:31]=2)[C@H:26]([NH:25][C:24]([O:23][CH:21]([CH3:22])[CH3:20])=[O:41])[CH2:27][C@@H:28]1[CH3:40])(=[O:39])[CH3:38]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 2773500Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 67195169methyl 4-((2S,4R)-1-acetyl-4-((isopropoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoateYield 82%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 18456801dichloropalladium DCMCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (0.355 g, 1.354 mmol), 1-methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Example 4) (0.5 g, 1.354 mmol), a saturated NaHCO3 aqueous solution (1.5 mL, 1.354 mmol) and bis(diphenylphosphino)ferrocene]dichloropalladium(II)-DCM adduct (0.111 g, 0.135 mmol) then filled with 1,4-dioxane (7 mL). The resulting mixture was degassed by bubbling nitrogen in to it, stirred at 100° C. for 1 hr under microwave irradiation then cooled to room temperature. The reaction mixture was filtered through celite and concentrated in vacuo. The residue was partitioned between EtOAC (30 mL) and water (30 mL) and the layers were separated. The organic phase was washed with brine (25 mL) dried over MgSO4 and concentrated in vacuo to give methyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (0.47 g, 1.11 mmol, 82%) which was used in the next step without further purification

Workup

  1. customThe resulting mixture was degassed
  2. customby bubbling nitrogen in to it
  3. temperaturethen cooled to room temperature
  4. filtrationThe reaction mixture was filtered through celite and
  5. concentrationconcentrated in vacuo
  6. customThe residue was partitioned between EtOAC (30 mL) and water (30 mL)
  7. customthe layers were separated
  8. washThe organic phase was washed with brine (25 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dc6dd45ab3ef4b249ee9ea37bf6e169e
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…