Diethyl Ether → 7-(5-Acetyl-2-trifluoromethoxy-phenyl)-1-ethyl-4,4,6-trimethyl-3,4-dihydro-1h-quinolin-2-one

HRID 1869548Notes

Reaction equation

HRID 1869548 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([CH3:26])=[C:10]([C:13]3[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=3[O:21][C:22]([F:25])([F:24])[F:23])[CH:16]=[O:17])[CH:11]=2)[C:6]([CH3:28])([CH3:27])[CH2:5][C:4]1=[O:29])[CH3:2].[CH3:30][Mg]Br.CCOCC.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C1COCC1.ClCCl>[C:16]([C:15]1[CH:18]=[CH:19][C:20]([O:21][C:22]([F:23])([F:24])[F:25])=[C:13]([C:10]2[CH:11]=[C:12]3[C:7]([C:6]([CH3:28])([CH3:27])[CH2:5][C:4](=[O:29])[N:3]3[CH2:1][CH3:2])=[CH:8][C:9]=2[CH3:26])[CH:14]=1)(=[O:17])[CH3:30]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 159087TriacetoxyperiodinaneHCID 112234493-(1-Ethyl-4,4,6-trimethyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl)-4-trifluoromethoxy-benzaldehydeHCID 178418573HCID 178418573, compound

Product 1

HCID 686663477-(5-Acetyl-2-trifluoromethoxy-phenyl)-1-ethyl-4,4,6-trimethyl-3,4-dihydro-1h-quinolin-2-oneYield 75%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of Compound 2A (270 mg, 0.66 mmol) in 3 mL of dry THF was cooled to −78° C. and treated with a 3M solution of methyl magnesium bromide in ether (0.24 mL, 0.73 mmol). The reaction mixture was allowed to slowly warm to room temperature where it was quenched with 10 mL of a saturated ammonium chloride solution. The reaction mixture was then passed through a 10 mL SPE (solid phase extraction) column which was further washed with dichloromethane. The eluant was collected and stripped to give crude alcohol which was then dissolved in dichloromethane and treated with Dess-Martin reagent (336 mg, 0.79 mmol) and stirred at room temperature overnight. The reaction was quenched with 4 mL of saturated sodium thiosulfate solution and 4 mL of saturated sodium bicarbonate solution, the reaction mixture was stirred until clear. The reaction mixture was passed through another SPE and eluted with dichloromethane, removal of solvent yielded crude ketone which was purified with flash chromatography (25% EtOAc/hexane) to yield 207 mg (75%) of the desired product (Compound 19A) and a white solid. MS (electrospray): mass calculated for C23H24F3NO3, 419.17; m/z found 420.2 [M+H]+.

Workup

  1. customwas quenched with 10 mL of a saturated ammonium chloride solution
  2. extractionThe reaction mixture was then passed through a 10 mL SPE (solid phase extraction) column which
  3. washwas further washed with dichloromethane
  4. customThe eluant was collected
  5. customto give crude alcohol which
  6. customThe reaction was quenched with 4 mL of saturated sodium thiosulfate solution and 4 mL of saturated sodium bicarbonate solution
  7. stirringthe reaction mixture was stirred until clear
  8. washeluted with dichloromethane, removal of solvent
  9. customyielded crude ketone which
  10. customwas purified with flash chromatography (25% EtOAc/hexane)

Sources & evidence

ORD record
ord-ac76bdb1a7ea4a48b3e6a9efce858884
Source dataset
uspto-grants-2009_12
Patent number
US07638533B2

Reaction notes

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