Triphenylphosphine → 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid

HRID 1072508노트

반응식

HRID 1072508 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[C:12](=[C:13]([Cl:19])[CH:14]=[C:15]([Cl:18])[CH:16]=3)[CH2:11][N:10]([CH3:20])[CH2:9]2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C]=[O:41].CN([CH:45]=[O:46])C.C1C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:18][C:15]1[CH:16]=[C:17]2[C:12](=[C:13]([Cl:19])[CH:14]=1)[CH2:11][N:10]([CH3:20])[CH2:9][CH:8]2[C:5]1[CH:6]=[CH:7][C:2]([C:45]([OH:46])=[O:41])=[CH:3][CH:4]=1

참가 물질

7

반응물 4

HCID 11776TriphenylphosphineHCID 101772114-(4-Bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline2회HCID 19608675Benzene dimethylformamideHCID 178418416HCID 178418416, 화합물2회

생성물 1

HCID 99238294-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid

시약·촉매·용매 2

HCID 24290Palladium Chloride촉매HCID 178418397HCID 178418397, 화합물촉매2회

반응 조건

온도
120 °C

실험 절차

5.57 g (15 mmol) of 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3) was dissolved in 150 ml of abs. DMF/benzene (1:1). After the solution was degassed, under argon 1.18 g (4.5 mmol) of triphenylphosphine and 1.17 g (9 mmol) of Ca(HCO2)2 were added. After renewed flushing with argon, 867 mg (0.75 mmol) of Pd(PPh3)4 was added and carbon monoxide was passed into the solution. The mixture was stirred at 120° C. After six hours at 120° C. and standing overnight under argon, a further 867 mg (0.75 mmol) of Pd(PPh3)4 was added and stirring at 120° C. and passing carbon monoxide into the solution was continued for eight hours. After again standing overnight, 135 mg of PdCl2 was added and reaction was allowed to take place under the same conditions. For workup, the solvent was removed in vacuo and the residue was taken up in ethyl acetate. Three extractions with 2 N NaOH were carried out. The combined aqueous phases were adjusted to pH 6 with 6 N HCl and extracted three times with ethyl acetate. The organic phases were dried with MgSO4 and freed of solvent. The residue was purified on silica gel using a dichloromethane/methanol mixture, resulting in 420 mg of the title compound (Rt=4.025 min (method A); MS(Cl+)=336.1/338.1).

후처리

  1. additionwere added
  2. additionwas added
  3. waitstanding overnight under argon
  4. stirringstirring at 120° C.
  5. waitwas continued for eight hours
  6. waitAfter again standing overnight
  7. customreaction
  8. customFor workup, the solvent was removed in vacuo
  9. extractionThree extractions with 2 N NaOH
  10. extractionextracted three times with ethyl acetate
  11. dry with materialThe organic phases were dried with MgSO4
  12. customThe residue was purified on silica gel using a dichloromethane/methanol mixture

출처 및 근거

ORD 기록
ord-b463f1cb1aaa447f92e365fb2d8cc22d
출처 데이터셋
uspto-grants-2005_06
특허 번호
US06911453B2

반응 노트

불러오는 중…