Water → (+/-)-4-[[4-(3-chlorophenyl)-1,2-dihydro-1-methyl-2-oxo-6-quinolinyl]hydroxy(1-methyl-1H-imidazol-5-yl)methyl]benzaldehyde

HRID 346989Notes

Reaction equation

HRID 346989 reaction equation
I[CH3:2].Cl.[Cl:4][C:5]1[CH:6]=[C:7]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:21]([OH:36])([C:30]4[N:34]([CH3:35])[CH:33]=[N:32][CH:31]=4)[C:22]4[CH:29]=[CH:28][C:25]([CH:26]=[O:27])=[CH:24][CH:23]=4)[CH:19]=3)[NH:14][C:13](=[O:37])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1.O>CC[N+](CC1C=CC=CC=1)(CC)CC.[Cl-].[OH-].[Na+].C1COCC1>[Cl:4][C:5]1[CH:6]=[C:7]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:21]([OH:36])([C:30]4[N:34]([CH3:35])[CH:33]=[N:32][CH:31]=4)[C:22]4[CH:29]=[CH:28][C:25]([CH:26]=[O:27])=[CH:24][CH:23]=4)[CH:19]=3)[N:14]([CH3:2])[C:13](=[O:37])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1

Participants

7

Reactant 3

HCID 962WaterHCID 6328Methyl iodideHCID 21082104(+/-)-4-[[4-(3-chlorophenyl)-1,2-dihydro-2-oxo-6-quinolinyl]hydroxy(1-methyl-1H-imidazol-5-yl)methyl]benzaldehyde monohydrochloride

Product 1

HCID 10299684(+/-)-4-[[4-(3-chlorophenyl)-1,2-dihydro-1-methyl-2-oxo-6-quinolinyl]hydroxy(1-methyl-1H-imidazol-5-yl)methyl]benzaldehydeYield 32%

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

BTEAC (0.00395 mol), then iodomethane (0.00474 mol) were added to a solution of (±)-4-[[4-(3-chlorophenyl)-1,2-dihydro-2-oxo-6-quinolinyl]hydroxy(1-methyl-1H-imidazol-5yl)methyl]benzaldehyde monohydrochloride (described in Example B1) (0.00395 mol) in NaOH (1N) and THF (20 ml). The mixture was stirred at room temperature for 18 hours, poured out into H2O and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue (1.1 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.2; 15–40 μm). The pure fractions were collected and the solvent was evaporated. The residue (0.87 g) was crystallized from diethyl ether. The precipitate was filtered off and dried, yielding 0.61 g (32%) of (±)-4-[[4-(3-chlorophenyl)-1,2-dihydro-1-methyl-2-oxo-6-quinolinyl]hydroxy(1-methyl-1H-imidazol-5-yl)methyl]benzaldehyde, mp. 208° C.

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent was evaporated
  6. customThe residue (1.1 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.2; 15–40 μm)
  7. customThe pure fractions were collected
  8. customthe solvent was evaporated
  9. customThe residue (0.87 g) was crystallized from diethyl ether
  10. filtrationThe precipitate was filtered off
  11. customdried

Sources & evidence

ORD record
ord-df411440408a42dba154584c8840f70d
Source dataset
uspto-grants-2007_02
Patent number
US07173040B2

Reaction notes

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