Sodium Bicarbonate → HCID 67194868, compound

HRID 2366896Notes

Reaction equation

HRID 2366896 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1B1OC(C)(C)C(C)(C)O1)[C:5]([O:7][CH3:8])=[O:6].[CH3:21][CH:22]([O:24][C:25](=[O:42])[NH:26][C@H:27]1[C:36]2[C:31](=[CH:32][CH:33]=[C:34](Br)[CH:35]=2)[N:30]([C:38](=[O:40])[CH3:39])[C@@H:29]([CH3:41])[CH2:28]1)[CH3:23].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:38]([N:30]1[C:31]2[C:36](=[CH:35][C:34]([C:11]3[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=3[CH3:1])=[CH:33][CH:32]=2)[C@H:27]([NH:26][C:25]([O:24][CH:22]([CH3:23])[CH3:21])=[O:42])[CH2:28][C@@H:29]1[CH3:41])(=[O:40])[CH3:39]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 110870242-Methyl-4-methoxycarbonylphenylboronic acid, pinacol esterHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 67194868HCID 67194868, compoundYield 56.8%

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 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (0.449 g, 1.625 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), sodium bicarbonate (saturated 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. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 60% AcOEt in hexanes) gave methyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-3-methylbenzoate (337 mg, 0.769 mmol, 56.8%) as a light yellow solid.

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
  11. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 60% AcOEt in hexanes)

Sources & evidence

ORD record
ord-d2bd06be647749dabb60f1fd25f5253f
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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