2-Bromo-5-fluorobenzotrifluoride → (R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine

HRID 1868119

反応式

HRID 1868119 の反応式
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.Br[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[C:16]([F:19])([F:18])[F:17].CC([O-])(C)C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[F:15][C:12]1[CH:13]=[CH:14][C:9]([N:6]2[CH2:5][CH2:4][NH:3][C@H:2]([CH3:1])[CH2:7]2)=[C:10]([C:16]([F:17])([F:18])[F:19])[CH:11]=1

参加物

6

反応物 3

HCID 5209832-Bromo-5-fluorobenzotrifluorideHCID 73304342-Methylpiperazine, (R)-HCID 23676156Sodium t-butoxide

生成物 1

HCID 68554948(R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine収率 82.4%

試薬・触媒・溶媒 2

HCID 634876Binap, (A+-)-触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
100 °C

実験手順

(R)-2-methyl-piperazine (3.5 g, 34.9 mmol), 2-bromo-5-fluoro benzotrifluoride (7.74 g, 31.7 mmol), BINAP (0.59 g, 0.95 mmol), tBuONa (4.58 g, 47.65 mmol) and Pd2(dba)3 (0.29 g, 0.32 mmol) were mixed in the flask and purged with N2. Anhydrous toluene (50 mL) was added and purged with N2 again. The resulting mixture was heated in an oil bath at 100° C. under N2 for 3 hours. The mixture was cooled to room temperature, diluted with dichloromethane (150 mL), washed with H2O (30 mL) first, then washed with saturated brine (30 mL). The combined organic layer was dried over Na2SO4, concentrated down under reduced pressure to give a brown color liquid as crude. The crude product was purified on silica gel column eluted with 5-10% MeOH in DCM to give (3R)-1-[4-fluoro-2-(trifluoromethyl)phenyl]-3-methylpiperazine as a light yellow oil (6.85 g, 82%).

後処理

  1. custompurged with N2
  2. additionAnhydrous toluene (50 mL) was added
  3. custompurged with N2 again
  4. temperatureThe mixture was cooled to room temperature
  5. additiondiluted with dichloromethane (150 mL)
  6. washwashed with H2O (30 mL) first
  7. washwashed with saturated brine (30 mL)
  8. dry with materialThe combined organic layer was dried over Na2SO4
  9. concentrationconcentrated down under reduced pressure
  10. customto give a brown color liquid as crude
  11. customThe crude product was purified on silica gel column
  12. washeluted with 5-10% MeOH in DCM

出典と根拠

ORDレコード
ord-d533b43a677146f8923ac74e7be809ee
出典データセット
uspto-grants-2009_12
特許番号
US07632838B2

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