Sodium Carbonate → tert-Butyl-5-(4-(ethoxycarbonyl)phenyl)-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1891231

반응식

HRID 1891231 반응식
O=[C:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].FC(F)(F)S(N(C1C=CC(Cl)=CN=1)S(C(F)(F)F)(=O)=O)(=O)=O.[CH2:47]([O:49][C:50]([C:52]1[CH:57]=[CH:56][C:55](B(O)O)=[CH:54][CH:53]=1)=[O:51])[CH3:48].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.C(#N)C>[C:11]([O:10][C:8]([N:4]1[CH2:3][C:2]([C:55]2[CH:56]=[CH:57][C:52]([C:50]([O:49][CH2:47][CH3:48])=[O:51])=[CH:53][CH:54]=2)=[CH:7][CH2:6][CH2:5]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

참가 물질

8

반응물 5

HCID 10340Sodium CarbonateHCID 388544N-(5-chloropyridin-2-yl)-1,1,1-trifluoro-N-trifluoromethanesulfonylmethanesulfonamideHCID 2733832Lithium HexamethyldisilazideHCID 27343504-Ethoxycarbonylphenylboronic acidHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylate

생성물 1

HCID 68488371tert-Butyl-5-(4-(ethoxycarbonyl)phenyl)-3,6-dihydropyridine-1(2H)-carboxylate

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a cooled (−78° C.) solution of tert-butyl 3-oxopiperidine-1-carboxylate (5.00 grams, 25.1 mmol) in anhydrous THF (40 mL) was added lithium bis(trimethylsilyl)amide (28.9 mL, 1.0 M in THF, 28.9 mmol) dropwise. After 90 min, a solution of 2-[N,N-bis(trifluoromethylsulfonyl)amino]5-chloropyridine (10.35 g, 26.3 mmol) in THF (20 mL) was added, and the resulting mixture was allowed to warm slowly to ambient temperature overnight, at which point it was quenched by pouring into sat aq NaHCO3. The mixture was extracted with EtOAc. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting enol triflate was filtered though silica gel, concentrated in vacuo, and used without further purification. To a flask containing the unpurified enol triflate were added 4-ethoxycarbonylphenylboronic acid (6.33 g, 32.6 mmol) and trans-dichlorobis(triphenylphosphine) palladium (II) (890 mg, 1.26 mmol). Acetonitrile (90 mL) and sodium carbonate (63 mL, 1.0 M aqueous, 63.0 mmol) were added, and the resulting mixture was degassed via nitrogen sparge. The reaction mixture was stirred at 70° C. for 3 h, then was allowed to cool to room temperature and was poured into water. The mixture was extracted with EtOAc, and the organic phase was concentrated in vacuo. Purification by chromatography on silica gel (0 to 10% EtOAc in hexanes, then 10 to 100% EtOAc) provided the title compound: LCMS m/z 276.0 [M-tBu]+; 1H NMR (500 MHz, CDCl3) δ 8.00 (d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 6.34-6.32 (m, 1H), 4.37 (q, J=7.0 Hz, 2H), 4.30-4.24 (br m, 2H), 3.58-3.54 (m, 2H), 2.34 (br m, 2H), 1.50 (s, 9H), 1.39 (t, J=7.0 Hz, 3H).

후처리

  1. customwas quenched
  2. additionby pouring
  3. extractionThe mixture was extracted with EtOAc
  4. customThe organic phase was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. filtrationThe resulting enol triflate was filtered though silica gel
  8. concentrationconcentrated in vacuo
  9. customused without further purification
  10. additionTo a flask containing the unpurified enol triflate
  11. customthe resulting mixture was degassed via nitrogen
  12. customsparge
  13. temperatureto cool to room temperature
  14. additionwas poured into water
  15. extractionThe mixture was extracted with EtOAc
  16. concentrationthe organic phase was concentrated in vacuo
  17. customPurification by chromatography on silica gel (0 to 10% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-54787c7d7fc64903b031462c36965d97
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507512B2

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