Tetrabutylammonium Fluoride → HCID 67157630, compound

HRID 221538Notes

Reaction equation

HRID 221538 reaction equation
ClC1C=NC2C(C=1[N+]([O-])=O)=CC=CC=2.N[C@@H](C(F)(C)C)CO.[Si]([O:30][CH2:31][C@H:32]([N:37]1[C:49]2[C:48]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[N:42]=[CH:41][C:40]=2[N:39]=[C:38]1[CH2:50]Cl)[C:33]([F:36])([CH3:35])[CH3:34])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(Cl)Cl.C1COCC1>[F:36][C:33]([C@@H:32]1[N:37]2[C:49]3[C:48]4[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=4)[N:42]=[CH:41][C:40]=3[N:39]=[C:38]2[CH2:50][O:30][CH2:31]1)([CH3:35])[CH3:34]

Participants

7

Reactant 4

HCID 2724141Tetrabutylammonium Fluoride2×HCID 54483735HCID 54483735, compoundHCID 66619887HCID 66619887, compoundHCID 671571901-[(1S)-1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluoro-2-methylpropyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline

Product 1

HCID 67157630HCID 67157630, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

The title compound was prepared from 3-chloro-4-nitroquinoline and (2R)-2-amino-3-fluoro-3-methylbutan-1-ol following Parts A through G listed for the preparation of Example 1 with the following modification. In Part E, a solution of 1-[(1S)-1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluoro-2-methylpropyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline (1.63 g, 3.78 mmol) in CH2Cl2 (100 mL) was cooled to −78° C. A solution of tetrabutylammonium fluoride in THF (4.16 mL of 1.0 M) was added, and the reaction mixture was allowed to warm to room temperature overnight. The solution was cooled again to −78° C., and additional tetrabutylammonium fluoride in THF (0.4 mL) was added, and the reaction mixture was allowed to warm to room temperature and stirred for one day. The reaction mixture was washed with saturated aqueous NaHCO3 followed by brine (4×50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (SiO2, eluting with 3% methanol in CHCl3) provided (11R)-11-(1-fluoro-1-methylethyl)-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline as a light yellow foam.

Workup

  1. customlisted for the preparation of Example 1 with the following modification
  2. temperatureThe solution was cooled again to −78° C.
  3. temperatureto warm to room temperature
  4. washThe reaction mixture was washed with saturated aqueous NaHCO3
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. washChromatography (SiO2, eluting with 3% methanol in CHCl3)

Sources & evidence

ORD record
ord-5108099d61d34ee98c5101a24bb60424
Source dataset
uspto-grants-2012_06
Patent number
US08207162B2

Reaction notes

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