Triphenylphosphine → [2-(4,5-Difluoro-2-methoxy-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 1513984노트

반응식

HRID 1513984 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13](=[O:29])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F-].[Cs+].Br[C:78]1[CH:83]=[C:82]([F:84])[C:81]([F:85])=[CH:80][C:79]=1[O:86][CH3:87]>CC(O)=O.CC(O)=O.[Pd].C(#N)C>[F:85][C:81]1[C:82]([F:84])=[CH:83][C:78]([C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:9]=2[C:13]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=2)=[O:29])=[C:79]([O:86][CH3:87])[CH:80]=1

참가 물질

8

반응물 5

HCID 11776TriphenylphosphineHCID 25953Cesium fluoride2회HCID 2733548Bis(pinacolato)diboraneHCID 27362621-Bromo-4,5-difluoro-2-methoxybenzeneHCID 11685250Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)benzoyl]-naphthalen-2-yl ester

생성물 1

HCID 11203380[2-(4,5-Difluoro-2-methoxy-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

시약·촉매·용매 2

HCID 4144353Palladium (II) acetate촉매2회HCID 6342Acetonitrile용매

실험 절차

Add trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (2.3 gm, 4.2 mmoles), bis(pinacolato)diboron (1.3 gm, 5.1 mmoles), palladium II acetate (97 mg, 0.4 mmoles), triphenylphosphine (222 mg, 0.84 mmoles) and cesium fluoride (2.1 gm, 14.1 mmoles) in a 250 ml round bottom flask under nitrogen and add 100 ml of anhydrous acetonitrile. Stir and heat to reflux for 2 hours. Allow the mixture to cool and to this mixture add 2-bromo-4,5-difluoroanisole (2.8 gm, 12.5 mmoles), palladium II acetate (96 mg, 0.43 mmoles) triphenylphosphine (222 mg, 0.84 moles) and cesium fluoride (1.8 gm, 12.2 mmoles). Reflux the mixture for 18 hours and filter through Celite. Evaporate the solvent and pass through an SCX column eluting the product with 2N ammonia/methanol. The product is purified on a silica column eluting with a gradient of 25% THF/hexane to 5% 2N ammonia/methanol in 25% THF/Hexane. LC/MS gives a peak with the proper mass.

후처리

  1. temperatureheat
  2. temperatureto reflux for 2 hours
  3. temperatureAllow the mixture to cool and to this mixture
  4. temperatureReflux the mixture for 18 hours
  5. filtrationfilter through Celite
  6. customEvaporate the solvent and pass through an SCX column
  7. washeluting the product with 2N ammonia/methanol
  8. customThe product is purified on a silica column
  9. washeluting with a gradient of 25% THF/hexane to 5% 2N ammonia/methanol in 25% THF/Hexane
  10. customLC/MS gives a peak with the proper mass

출처 및 근거

ORD 기록
ord-be5973d18bf04ca48b8c0e95e7ac6997
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217032B2

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