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 1629724ノート

反応式

HRID 1629724 の反応式
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]

参加物

10

反応物 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

生成物 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

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒HCID 6386tert-Butanol溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
100 °C

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-74a3ba2666124bf99eca54a2ebb33ed4
出典データセット
uspto-grants-2014_07
特許番号
US08791100B2

反応ノート

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