Methanol → 2-methyl-6,7-dihydroquinolin-8(5H)-one

HRID 2099432Notes

Reaction equation

HRID 2099432 reaction equation
C(=[C:8]1[C:17]2[N:16]=[C:15]([CH3:18])[CH:14]=[CH:13][C:12]=2[CH2:11][CH2:10][CH2:9]1)C1C=CC=CC=1.CO.[O:21]=[O+][O-]>ClCCl>[CH3:18][C:15]1[CH:14]=[CH:13][C:12]2[CH2:11][CH2:10][CH2:9][C:8](=[O:21])[C:17]=2[N:16]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 24823OzoneHCID 688929538-Benzylidene-2-methyl-5,6,7,8-tetrahydro-quinoline

Product 1

HCID 541706492-methyl-6,7-dihydroquinolin-8(5H)-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Intermediate 200A2 in dichloromethane (100 mL)/methanol (200 mL) was cooled to −78° C. Ozone was passed through the mixture for 1-2 h until the mixture had a light blue color. The reaction mixture was purged with nitrogen followed by the addition of dimethyl sulfide (10 mL). The mixture was stirred for 30 m and evaporated. The residue was partitioned between ether and 1M HCl. The organic layer was extracted with 1N HCl (2×) and the acidic, aqueous layers were pooled, washed with ether (3×), cooled with crushed ice, and carefully basified with solid NaOH. The basic layer was extracted with chloroform, freed of solvent, and the residue was passed through a column of SiO2 with 80% ethyl acetate/hexane to give impure Intermediate 200A3 as a yellow solid. Further purification of this mixture was conducted by oxidation of the minor product: (˜3%) 8-oxo-5,6,7,8-tetrahydro-quinoline-2-carbaldehyde in formic acid (15 mL) at 0° C. by dropwise addition of H2O2 (2.1 mL, 30% solution). The mixture was stirred for 1.5 h, quenched with crushed ice, diluted with chloroform, and basified with 2 M NaOH to pH>8. The chloroform layer was dried, filtered and evaporated to give pure 2-methyl-6,7-dihydro-5H-quinolin-8-one (Intermediate 200A3), 15.1 g (˜50% over two steps).

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. additionfollowed by the addition of dimethyl sulfide (10 mL)
  3. customevaporated
  4. customThe residue was partitioned between ether and 1M HCl
  5. extractionThe organic layer was extracted with 1N HCl (2×)
  6. washwashed with ether (3×)
  7. temperaturecooled with crushed ice
  8. extractionThe basic layer was extracted with chloroform

Sources & evidence

ORD record
ord-923368371e0a4c4198be2c3a6a8fdc9e
Source dataset
uspto-grants-2009_08
Patent number
US07569584B2

Reaction notes

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