Ethyl Bromide → 5-(4-(Difluoromethoxy)-2-ethoxy-3-methoxyphenyl)isoindolin-1-one

HRID 2171096ノート

反応式

HRID 2171096 の反応式
BrC1C(O)=C(OC)C(OC(F)F)=CC=1.C(=O)([O-])[O-].[K+].[K+].C(Br)C.Br[C:25]1[CH:30]=[CH:29][C:28]([O:31][CH:32]([F:34])[F:33])=[C:27]([O:35][CH3:36])[C:26]=1[O:37][CH2:38][CH3:39].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:54]2[CH:55]=[C:56]3[C:60](=[CH:61][CH:62]=2)[C:59](=[O:63])[NH:58][CH2:57]3)O1>C(#N)C.CN(C)C=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:33][CH:32]([F:34])[O:31][C:28]1[CH:29]=[CH:30][C:25]([C:54]2[CH:55]=[C:56]3[C:60](=[CH:61][CH:62]=2)[C:59](=[O:63])[NH:58][CH2:57]3)=[C:26]([O:37][CH2:38][CH3:39])[C:27]=1[O:35][CH3:36]

参加物

10

反応物 6

HCID 6332Ethyl BromideHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 674668041-Bromo-4-(difluoromethoxy)-2-ethoxy-3-methoxybenzeneHCID 674670406-Bromo-3-(difluoromethoxy)-2-methoxyphenol

生成物 1

HCID 674629765-(4-(Difluoromethoxy)-2-ethoxy-3-methoxyphenyl)isoindolin-1-one収率 13%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
80 °C

実験手順

To a stirring solution of 6-bromo-3-(difluoromethoxy)-2-methoxyphenol (200 mg, 0.74 mmol) in acetonitrile (10 mL) was added potassium carbonate (307 mg, 2.23 mmol) and ethyl bromide (0.6 mL, 2.23 mmol) and the resultant reaction mixture was heated to 80° C. for 2 h. The reaction mixture was cooled to RT, filtered through celite and the filtrate was concentrated under reduced pressure to afford 200 mg of crude product, 1-Bromo-4-difluoromethoxy-2-ethoxy-3-methoxy-benzene, as a solid. A stirring solution of 1-bromo-4-(difluoromethoxy)-2-ethoxy-3-methoxybenzene (200 mg, 0.673 mmol) in N,N-dimethylformamide (5 mL) was purged with argon for 1 h, to this cesium carbonate (656 mg, 2.019 mmol), tetrakis(triphenylphosphine) palladium(0) (38 mg, 0.033 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (209 mg, 0.807 mmol) were added and the resultant reaction mixture was heated to 80-90° C. for 3 h. The reaction mixture was cooled to RT, filtered and the filtrate was diluted with water and extracted with ethyl acetate (3×). The combined ethyl acetate layer was washed with brine and dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether) afforded the title compound as a solid (30 mg, 13%).

後処理

  1. customthe resultant reaction mixture
  2. temperatureThe reaction mixture was cooled to RT
  3. filtrationfiltered through celite
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customto afford 200 mg of crude product, 1-Bromo-4-difluoromethoxy-2-ethoxy-3-methoxy-benzene
  6. additionwere added
  7. customthe resultant reaction mixture
  8. temperaturewas heated to 80-90° C. for 3 h
  9. temperatureThe reaction mixture was cooled to RT
  10. filtrationfiltered
  11. additionthe filtrate was diluted with water
  12. extractionextracted with ethyl acetate (3×)
  13. washThe combined ethyl acetate layer was washed with brine
  14. dry with materialdried over anhydrous sodium sulphate
  15. concentrationconcentrated under reduced pressure
  16. customPurification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether)

出典と根拠

ORDレコード
ord-ff9bebd396da48bab6ad2cab4e78b7f3
出典データセット
uspto-grants-2015_06
特許番号
US09051290B2

反応ノート

読み込み中…