Sulfuric Acid → HCID 67171514, compound

HRID 1506335Notes

Reaction equation

HRID 1506335 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[N:13][OH:14])[CH2:8][CH2:7][CH2:6]2.C([Li])CCC.[CH2:20]([C:23]1[CH:32]=[CH:31][C:26]([C:27](OC)=O)=[CH:25][CH:24]=1)[CH2:21][CH3:22].OS(O)(=O)=O>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]1=[N:13][O:14][C:27]([C:26]3[CH:31]=[CH:32][C:23]([CH2:20][CH2:21][CH3:22])=[CH:24][CH:25]=3)=[C:8]1[CH2:7][CH2:6]2

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 52161626-Methoxy-1-tetralone oxime2×HCID 12861010Methyl 4-propylbenzoateHCID 178418339Butyllithium

Product 1

HCID 67171514HCID 67171514, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To 6-methoxy-3,4-dihydronaphthalen-1(2H)-one oxime (Intermediate 2, 0.483 g, 2.52 mmol) in 4 mL of THF, cooled to 0° C. was added butyllithium (2.5 M, 2.020 mL, 5.05 mmol) dropwise over a period of 3 min. The contents were stirred at 0° C. for 30 min. A solution of methyl 4-propylbenzoate (Preparation 9A, 0.3 g, 1.683 mmol) dissolved in 2 mL of THF was added over a period of 3 min. The pale yellow reaction mixture was allowed to come to room temperature and stirred for 20 min. at room temperature. To the reaction mixture was added 0.5 mL of conc. H2SO4 dropwise over a period of 3 min. at 0° C. The reaction was allowed to come to room temperature over a period of 10 min. and stirred at room temperature for 40 min. The reaction mixture was concentrated under reduced pressure and partitioned between ethyl acetate (25 mL) and water (10 mL). The ethyl acetate layer was washed with sat. aq. sodium bicarbonate (15 mL), dried over sodium sulfate, concentrated and purified by silica gel column chromatography employing hexane/ethyl acetate. Product containing fractions were collected and concentrated to yield 7-methoxy-3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazole (0.355 g, 1.111 mmol, 66.0% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.93 (d, J=8.28 Hz, 1H) 7.69 (d, J=8.28 Hz, 2H) 7.30 (d, J=8.28 Hz, 2H) 6.83-6.91 (m, 2H) 3.86 (s, 3H) 2.95-3.06 (m, 4H) 2.61-2.68 (m, 2H) 1.62-1.74 (m, J=7.47, 7.47, 7.47, 7.47, 7.28 Hz, 2H) 0.97 (t, 3H).

Workup

  1. additionwas added over a period of 3 min
  2. customto come to room temperature
  3. stirringstirred for 20 min. at room temperature
  4. waitto come to room temperature over a period of 10 min.
  5. stirringstirred at room temperature for 40 min
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. custompartitioned between ethyl acetate (25 mL) and water (10 mL)
  8. washThe ethyl acetate layer was washed with sat. aq. sodium bicarbonate (15 mL)
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. custompurified by silica gel column chromatography
  12. additionProduct containing fractions
  13. customwere collected
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-c5017ce713a94d40baa9ce171ec2130d
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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