Sodium Bicarbonate → methyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-3-methylbenzoate

온도

100 °C

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.

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)

ORD 기록

ord-d2bd06be647749dabb60f1fd25f5253f

출처 데이터셋

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08697725B2