4-(Trifluoromethoxy)aniline → 8-Methyl-2-(4-trifluoromethoxy-phenyl)-2-aza-spiro[4.5]dec-7-en-1-one

HRID 2092656Notes

Reaction equation

HRID 2092656 reaction equation
[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][CH:5]=1.CO[CH2:15][CH2:16][C:17]12[CH2:24][CH2:23][C:20]([CH3:25])([CH2:21][CH2:22]1)[O:19][C:18]2=O.[Cl-].C[Al+]C>C1(C)C=CC=CC=1>[CH3:25][C:20]1[CH2:23][CH2:24][C:17]2([C:18](=[O:19])[N:8]([C:7]3[CH:9]=[CH:10][C:4]([O:3][C:2]([F:11])([F:12])[F:1])=[CH:5][CH:6]=3)[CH2:15][CH2:16]2)[CH2:22][CH:21]=1

Participants

5

Reactant 3

HCID 6008484-(Trifluoromethoxy)anilineHCID 16686359Dimethylalumanylium chlorideHCID 665778854-(2-Methoxy-ethyl)-1-methyl-2-oxa-bicyclo[2.2.2]octan-3-one

Product 1

HCID 665778548-Methyl-2-(4-trifluoromethoxy-phenyl)-2-aza-spiro[4.5]dec-7-en-1-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

4-(Trifluoromethoxy)-aniline (0.065 mL, [CAS Reg. No. 461-82-5]) was added to a solution of 4-(2-methoxy-ethyl)-1-methyl-2-oxa-bicyclo[2.2.2]octan-3-one (64 mg, obtained in example 59, step 1) in toluene (5 mL). The mixture was stirred for 10 minutes at r.t. Then, dimethylaluminiumchloride (1M in hexane, 0.65 mL) was added dropwise over a period of 5 minutes. The reaction mixture was stirred at reflux for 3 hours. The reaction mixture was cooled, poured into ice/water and extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give 8-methyl-2-(4-trifluoromethoxy-phenyl)-2-aza-spiro[4.5]dec-7-en-1-one as a light yellow solid as the main product (81 mg, 77%). MS (m/e)=326.4 [MH+]. From this reaction, a small amount of (5α,8α)-8-hydroxy-8-methyl-2-(4-trifluoromethoxy-phenyl)-2-aza-spiro[4.5]decan-1-one (see example 57) was also isolated (6 mg, 5%).

Workup

  1. stirringThe reaction mixture was stirred
  2. temperatureat reflux for 3 hours
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted two times with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-f356bfe33bd645b7807e8904f0a3c24d
Source dataset
uspto-grants-2013_05
Patent number
US08440710B2

Reaction notes

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