Imidazole → 6,7-Dimethyl 5-methoxy-8-[[tris(1-methylethyl)silyl]oxy]-6,7-quinolinedicarboxylate

HRID 853693Notes

Reaction equation

HRID 853693 reaction equation
N1C=CN=[CH:2]1.Cl[Si:7]([CH:14]([CH3:16])[CH3:15])([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9].[CH3:17][O:18][C:19]([C:21]1[C:22]([OH:36])=[C:23]2[C:28](=[C:29]([OH:35])[C:30]=1[C:31]([O:33][CH3:34])=[O:32])[N:27]=[CH:26][CH:25]=[CH:24]2)=[O:20].C([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[CH3:17][O:18][C:19]([C:21]1[C:22]([O:36][CH3:2])=[C:23]2[C:28](=[C:29]([O:35][Si:7]([CH:14]([CH3:16])[CH3:15])([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9])[C:30]=1[C:31]([O:33][CH3:34])=[O:32])[N:27]=[CH:26][CH:25]=[CH:24]2)=[O:20]

Participants

7

Reactant 5

HCID 795ImidazoleHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 139400Triisopropylsilyl chlorideHCID 135742180Dimethyl 5,8-dihydroxy-6,7-quinolinedicarboxylate

Product 1

HCID 589290076,7-Dimethyl 5-methoxy-8-[[tris(1-methylethyl)silyl]oxy]-6,7-quinolinedicarboxylateYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Imidazole (0.74 g, 10.8 mmol) and chlorotriisopropylsilane (TIPSCl, 1.15 g, 6.0 mmol) were added to 5,8-dihydroxy-quinoline-6,7-dicarboxylic acid dimethyl ester (prepared by the method in Oguchi, S. Bulletin of the Chemical Society of Japan 1974, 47, 1291, 1.5 g, 5.4 mmol) in 20 mL DMF. The reaction was stirred for 48 h at rt and then the reaction was partitioned between 0.5 L methyl t-butyl ether and 150 mL saturated aq. LiCl. The organic layer was dried over Na2SO4 and the solvent removed by rotary evaporation. The residue (1.4 g, 3.2 mmol) was redissolved in 25 mL DMF and treated with K2CO3 (0.66 g, 4.8 mmol) followed by methyl iodide (MeI, 0.6 g, 4.8 μL) at rt. After 2 h, the reaction mixture was concentrated and purified by introduction of the reaction mixture onto silica gel for flash chromatography (4/1 hexanes/ethyl acetate) to give 5-methoxy-8-triisopropylsilanyloxy-quinoline-6,7-dicarboxylic acid dimethyl ester (1.4 g, 59% overall yield): 1H NMR (CDCl3) δ 8.85 (d, 1H), 8.45 (d, 1H), 7.50 (dd, 1H), 4.05 (s, 3H), 3.95 (s, 3H), 3.90 (s, 3H), 1.45 (septet, 3H), 1.05 (d, 9H); MS: 448 (M+H).

Workup

  1. customprepared by the method in Oguchi, S
  2. customthe reaction was partitioned between 0.5 L methyl t-butyl ether and 150 mL saturated aq. LiCl
  3. dry with materialThe organic layer was dried over Na2SO4
  4. customthe solvent removed by rotary evaporation
  5. waitAfter 2 h
  6. concentrationthe reaction mixture was concentrated
  7. custompurified by introduction of the reaction mixture onto silica gel for flash chromatography (4/1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-86e64417dfa641e6a1593160519a6d74
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

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