Bromide ion → [(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethyl]-(3-[1,3]dioxolan-2-yl-4-methyl-phenyl)-amine

HRID 1629724노트

반응식

HRID 1629724 반응식
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([NH2:14])[C:10]([F:13])([F:12])[F:11])=[CH:5][C:4]=1[CH3:15].[Br-].Br[C:18]1[CH:19]=[CH:20][C:21]([CH3:29])=[C:22]([CH:24]2[O:28][CH2:27][CH2:26][O:25]2)[CH:23]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O.C1(C)C=CC=CC=1.C(O)(C)(C)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([NH:14][C:18]2[CH:19]=[CH:20][C:21]([CH3:29])=[C:22]([CH:24]3[O:25][CH2:26][CH2:27][O:28]3)[CH:23]=2)[C:10]([F:12])([F:13])[F:11])=[CH:5][C:4]=1[CH3:15]

참가 물질

10

반응물 5

HCID 259Bromide ionHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 57517340(S)-1-(4-chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamine hydrochlorideHCID 583744502-(5-Bromo-2-methylphenyl)-1,3-dioxolane

생성물 1

HCID 68258686[(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethyl]-(3-[1,3]dioxolan-2-yl-4-methyl-phenyl)-amine

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 6386tert-Butanol용매HCID 8857Ethyl Acetate용매2회

반응 조건

온도
100 °C

실험 절차

(S)-1-(4-Chloro-3-methyl-phenyl)-2,2,2-trifluoro-ethylamine hydrochloride (5.00 g, 19.22 mmol) was taken up in EtOAc and washed with saturated aqueous NaHCO3, water (3×) and brine (2×). The organic layer was dried over MgSO4, filtered and concentrated. To a solution of the residue and bromide INT 31 (6.08 g, 24.99 mmol) in toluene (83 mL) and tert-butanol (33 mL) was added XPhos (1.83 g, 3.84 mmol) followed by Cs2CO3 (18.79 g, 57.67 mmol). The mixture was degassed for 10 minutes and Pd(OAc)2 (0.43 g, 1.92 mmol) was added. The reaction mixture was stirred at 100° C. for 4 hours. The mixture was diluted with EtOAc and washed with H2O (3×). The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine (2×), dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (heptane/EtOAc) to afford INT 32.

후처리

  1. washwashed with saturated aqueous NaHCO3, water (3×) and brine (2×)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe mixture was degassed for 10 minutes
  6. washwashed with H2O (3×)
  7. extractionThe aqueous layer was extracted with EtOAc
  8. washThe combined organic layers were washed with brine (2×)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography on silica gel (heptane/EtOAc)
  13. customto afford INT 32

출처 및 근거

ORD 기록
ord-74a3ba2666124bf99eca54a2ebb33ed4
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791100B2

반응 노트

불러오는 중…