Toluene → Methyl 3-amino-6-bromo-2-(4-(methoxycarbonyl)phenyl)isonicotinate

HRID 2410738노트

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HRID 2410738 반응식
[NH2:1][C:2]1[C:11](Br)=[N:10][C:9]([Br:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:14][O:15][C:16]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)=[O:17].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>CO>[NH2:1][C:2]1[C:11]([C:21]2[CH:22]=[CH:23][C:18]([C:16]([O:15][CH3:14])=[O:17])=[CH:19][CH:20]=2)=[N:10][C:9]([Br:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

참가 물질

6

반응물 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 53419616Methyl 3-amino-2,6-dibromoisonicotinate

생성물 1

HCID 86663017Methyl 3-amino-6-bromo-2-(4-(methoxycarbonyl)phenyl)isonicotinate수율 34%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
120 °C

실험 절차

A mixture of methyl 3-amino-2,6-dibromoisonicotinate (5.00 g, 16.1 mmol), 4-methoxycarbonylphenylboronic acid (2.90 gm, 16.1 mmol), and tetrakis-(triphenylphosphine)palladium(0) (0.932 g, 0.807 mmol) in a flask was flushed with nitrogen. Toluene (70 mL), MeOH (14 mL), and a 2 N aqueous solution of sodium carbonate (18 mL, 37 mmol) were added and the reaction was heated in a 120° C. oil bath for 4 hr. The reaction mixture was partitioned between EtOAc and saturated aqueous sodium bicarbonate solution. The organic phase was separated, washed with saturated aqueous sodium bicarbonate, and brine. It was dried with sodium sulfate and the solvents removed. Flash silica gel chromatography (elution with hexane containing 10% EtOAc) afforded methyl 3-amino-6-bromo-2-(4-(methoxycarbonyl)phenyl)isonicotinate (2.0 gm). MS (ESI) m/z 365.0 and 367.0 (M+H). 1H NMR (CDCl3) δ ppm 8.15 (2H, d, J=8.24 Hz), 7.84 (1H, s), 7.71 (2H, d, J=8.24 Hz), 5.94 (2H, br. s.), 3.94 (6H, d, J=5.19 Hz).

후처리

  1. customwas flushed with nitrogen
  2. customThe reaction mixture was partitioned between EtOAc and saturated aqueous sodium bicarbonate solution
  3. customThe organic phase was separated
  4. washwashed with saturated aqueous sodium bicarbonate, and brine
  5. dry with materialIt was dried with sodium sulfate
  6. customthe solvents removed
  7. washFlash silica gel chromatography (elution with hexane containing 10% EtOAc)

출처 및 근거

ORD 기록
ord-0bcbd3aad0344fe88b6bc3d52b9363bf
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815840B2

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