Benzene, 1-bromo-4-(trifluoromethyl)- → HCID 89964488, compound

HRID 1846210Notes

Reaction equation

HRID 1846210 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2(O)[C:18]3[N:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[Mg].[H-].C([Al+]CC(C)C)C(C)C.BrC1C=CC(C(F)(F)F)=CC=1.[N:44]1C2C(=O)CCCC=2C=CC=1>C1COCC1>[F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2([NH2:44])[C:18]3[N:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-2×HCID 5462224MagnesiumHCID 117447776,7-Dihydro-5H-quinoline-8-oneHCID 21225700DiisobutylaluminumhydrideHCID 89964803HCID 89964803, compound

Product 1

HCID 89964488HCID 89964488, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

8-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydroquinolin-8-ol. To a solution of magnesium (515 mg, 21.19 mmol) in THF (50 mL) was added 1M diisobutylaluminum hydride in hexanes (0.14 mL, 0.140 mmol). The solution was stirred at room temperature. After 20 min., the reaction was treated with a 20% portion of 1-bromo-4-(trifluoromethyl)benzene (1.9 mL, 13.57 mmol). After stirring for 20 min., the solution went from clear to light brown. The remaining 1-bromo-4-(trifluoromethyl)benzene was added dropwise. The solution was stirred for 0.5 h and then cooled in a dry ice/acetone bath. After cooling for 1 h, the reaction was treated with a solution of 6,7-dihydroquinolin-8(5H)-one (1.0 g, 6.79 mmol) in THF (7 mL) dropwise over 10 min. The solution was allowed to warm to room temperature as the cooling bath expires. After stirring for 16 h, the reaction was quenched with sat'd NH4Cl. The reaction was poured into water and EtOAc. The aqueous layer was extracted with EtOAc (25 mL). The combined EtOAc layers were concentrated in vacuo and adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with 0-20% EtOAc in hexane, to provide the title compound as a colorless oil. MS (ESI pos. ion) m/z: 293.9 (MH+). 1H NMR (CDCl3) δ: 8.36-8.51 (m, 1H), 7.44-7.60 (m, 3H), 7.27 (s, 1H), 7.15-7.26 (m, 2H), 4.19 (s, 1H), 2.82-3.01 (m, 2H), 2.14-2.36 (m, 2H), 1.90 (dt, J=14.2, 4.5 Hz, 1H), 1.57-1.78 (m, 1H).

Workup

  1. stirringAfter stirring for 20 min.
  2. stirringThe solution was stirred for 0.5 h
  3. temperaturecooled in a dry ice/acetone bath
  4. temperatureAfter cooling for 1 h
  5. temperatureto warm to room temperature as the cooling bath
  6. stirringAfter stirring for 16 h
  7. customthe reaction was quenched with sat'd NH4Cl
  8. additionThe reaction was poured into water and EtOAc
  9. extractionThe aqueous layer was extracted with EtOAc (25 mL)
  10. concentrationThe combined EtOAc layers were concentrated in vacuo
  11. customchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
  12. washeluting with 0-20% EtOAc in hexane

Sources & evidence

ORD record
ord-8a21a67ec130419f9b701ae58ca77662
Source dataset
uspto-grants-2015_02
Patent number
US08952009B2

Reaction notes

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