Tetrahydrofuran → HCID 67331956, compound

HRID 1669645Notes

Reaction equation

HRID 1669645 reaction equation
C1COCC1.[CH3:6][O:7][C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=2)[N:9]=1.[F:19][C:20]([F:29])([F:28])[CH:21]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]1>CCCCCC>[CH3:6][O:7][C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:24]3([OH:27])[CH2:23][CH2:22][CH:21]([C:20]([F:28])([F:29])[F:19])[CH2:26][CH2:25]3)[CH:14]=2)[N:9]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 27774914-(Trifluoromethyl)cyclohexanoneHCID 106575386-Bromo-2-methoxyquinoline

Product 1

HCID 67331956HCID 67331956, compound

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a cold (−78° C.) anhydrous THF solution of 2-methoxy-6-bromoquinoline (1.16 g, 4.89 mmol) was added w-BuLi (2.05 mL of a 2.5 M solution in hexane, 5.13 mmol). The mixture was stirred at −78° C. under a nitrogen atmosphere for 15 min and 4-(trifluoromethyl)cyclohexanone (0.81 g, 4.89 mmol) was added slowly to the reaction. After addition was complete, the bath was allowed to warm to room temperature. The reaction mixture was quenched with saturated NH4Cl (aq) and extracted with EtOAc/hexanes. The organic layer was dried over Na2SO4 and evaporated in vacuo and the resultant residue was purified by flash chromatography on silica gel using gradient elution (0% to 20% EtOAc/hexanes, 150 mL; 20% to 35% EtOAc/hexanes, 204 mL; 35% to 75% EtOAc/hexanes, 381 mL) to provide Isomer A as the faster-moving isomer and Isomer B as the slower-moving isomer.

Workup

  1. additionAfter addition
  2. temperatureto warm to room temperature
  3. customThe reaction mixture was quenched with saturated NH4Cl (aq)
  4. extractionextracted with EtOAc/hexanes
  5. dry with materialThe organic layer was dried over Na2SO4
  6. customevaporated in vacuo
  7. customthe resultant residue was purified by flash chromatography on silica gel using gradient elution (0% to 20% EtOAc/hexanes, 150 mL; 20% to 35% EtOAc/hexanes, 204 mL; 35% to 75% EtOAc/hexanes, 381 mL)
  8. customto provide Isomer A as the faster-moving isomer and Isomer B as the slower-moving isomer

Sources & evidence

ORD record
ord-06718d7e76b84434a234d8190d4dd621
Source dataset
uspto-grants-2011_08
Patent number
US07989472B2

Reaction notes

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