Hydrochloric Acid → 3-methyl-6-(methyloxy)-2-phenyl-3,4-dihydro-1(2H)-naphthalenone

HRID 1992811Notes

Reaction equation

HRID 1992811 reaction equation
[CH3:1][CH:2]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1)[CH:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4](O)=[O:5].C(Cl)(=O)C(Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-].Cl>C(Cl)Cl>[CH3:1][CH:2]1[CH2:13][C:14]2[C:19](=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[C:4](=[O:5])[CH:3]1[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 685372223-Methyl-4-[3-(methyloxy)phenyl]-2-phenylbutanoic acid

Product 1

HCID 685394423-methyl-6-(methyloxy)-2-phenyl-3,4-dihydro-1(2H)-naphthalenone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 3-methyl-4-[3-(methyloxy)phenyl]-2-phenylbutanoic acid (4) (13 g, 45.7 mmol) in CH2Cl2 (300 mL) was added oxalyl chloride (12 mL, 137.1 mmol) at room temperature. The reaction mixture was stirred for 10 h and concentrated under reduced pressure to afford the crude acid chloride. The acid chloride was redissolved in CH2Cl2 (300 mL) and cooled to 5° C. Anhydrous aluminum chloride (9.2 g, 68.6 mmol) was added, portion-wise, over a period of 15 min. The resulting brown colored reaction mixture was stirred at 5° C. for 3 h under N2. The reaction mixture was poured onto 2 N HCl (400 mL), stirred for 15 min and the layers were separated. The aqueous phase was further extracted with CH2Cl2 (3×200 mL). The combined organic solution was washed with sat. NaHCO3 (1×150 mL), brine (1×100 mL), dried (Na2SO4) and then concentrated under reduced pressure to afford the crude product. The product was purified by SiO2 flash column chromatography using hexanes:EtOAc (9:1 to 4:1) as an eluent to afford 5.62 g (46% over 3 steps) of the title compound. 1H NMR (400 MHz, CDCl3): δ 8.03 (d, J1=8.00 Hz, 1H), 7.35-7.20 (m, 3H), 7.12 (d, J=8.00 Hz, 1H), 6.86 and 6.84 (dd, J1=12.0 Hz, J2=4.00 Hz, 1H), 6.73 (br.s, 1H), 3.87 (s, 3H), 3.34 (d, J=12.0 Hz, 1H), 3.03 and 3.0 (dd, J1=16.0 Hz, J2=4.0 Hz, 1H), 2.85 and 2.81 (dd, J1=16.0 Hz, J2=8.0 Hz, 1H), 2.53 (m, 1H), 0.95 (d, J=4.0 Hz, 3H). 6.84-6.78 (m, 3H), 4.32 (sextet, J=4.0 Hz, 1H), 3.82 (s, 3H), 3.25 and 3.21 (dd, J1=16.0 Hz, J2=8.0 Hz, 1H), 3.07 and 3.04 (dd, J1=16.0 Hz, J2=8.0 Hz, 1H), 1.71 (d, J=8.00 Hz, 1H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customto afford the crude acid chloride
  3. waitportion-wise, over a period of 15 min
  4. stirringThe resulting brown colored reaction mixture was stirred at 5° C. for 3 h under N2
  5. stirringstirred for 15 min
  6. customthe layers were separated
  7. extractionThe aqueous phase was further extracted with CH2Cl2 (3×200 mL)
  8. washThe combined organic solution was washed with sat. NaHCO3 (1×150 mL), brine (1×100 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated under reduced pressure
  11. customto afford the crude product
  12. customThe product was purified by SiO2 flash column chromatography

Sources & evidence

ORD record
ord-fbcb60df23424081a6505a967ce938b5
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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