Tetrahydrofuran → (11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinoline

HRID 549191Notes

Reaction equation

HRID 549191 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]([C@@H:15]([CH3:25])[CH2:16][O:17][Si](C(C)(C)C)(C)C)[C:13]([CH2:26]Cl)=[N:12][C:7]=3[CH:8]=[N:9][C:10]=2[CH:11]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.C([O-])([O-])=O.[K+].[K+]>CO.C(Cl)Cl.O.ClCCCl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]3[N:14]4[C@@H:15]([CH3:25])[CH2:16][O:17][CH2:26][C:13]4=[N:12][C:7]=3[CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 671574837-bromo-1-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline

Product 1

HCID 67157683(11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolineYield 48.5%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
1 °C

Procedure

A 2-L, three-necked, Morton flask, equipped with mechanical stirrer, was charged with 7-bromo-1-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline (38.0 g, 81.0 mmol) and 1,2-dichloroethane (900 mL) and the mixture was cooled to 1° C. A 1.0 M solution of tetrabutylammonium fluoride in THF (90 mL, 90 mmol) was slowly added over 1.5 hours. The reaction temperature was maintained at 1-2° C. during addition. The reaction was allowed to slowly warm to ambient temperature and stirring was continued for 2 days. The reaction was treated with saturated aqueous K2CO3 solution (500 mL) and H2O (400 mL). The layers were separated and the aqueous portion was extracted with CH2Cl2 (3×100 mL). The organic layers were combined and concentrated under reduced pressure to give a tan solid. Chromatography (SiO2, 0-6% methanol/CH2Cl2) gave 12.5 g of (11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline as an off-white solid which was used without further purification. A small sample was crystallized from acetonitrile to give white crystals, mp 207-209° C.

Workup

  1. temperatureThe reaction temperature was maintained at 1-2° C. during addition
  2. temperatureto slowly warm to ambient temperature
  3. customThe layers were separated
  4. extractionthe aqueous portion was extracted with CH2Cl2 (3×100 mL)
  5. concentrationconcentrated under reduced pressure
  6. customto give a tan solid

Sources & evidence

ORD record
ord-0264846545f342a38c0ca6f21185d072
Source dataset
uspto-grants-2011_05
Patent number
US07943609B2

Reaction notes

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