Chlorotrimethylsilane → HCID 58349465, compound

HRID 2090065Notes

Reaction equation

HRID 2090065 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Br:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([F:25])=[C:21]([F:24])[CH:22]=2)[N:17]=[CH:16][CH:15]=1.Cl[Si:27]([CH3:30])([CH3:29])[CH3:28].[NH4+].[Cl-]>C1COCC1.O.CCOC(C)=O>[Br:13][C:14]1[C:23]2[C:18](=[C:19]([Si:27]([CH3:30])([CH3:29])[CH3:28])[C:20]([F:25])=[C:21]([F:24])[CH:22]=2)[N:17]=[CH:16][CH:15]=1

Participants

9

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 58349441HCID 58349441, compoundHCID 178418339Butyllithium

Product 1

HCID 58349465HCID 58349465, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Diisopropylamine (0.770 mL, 5.41 mmol) was added dropwise to nBuLi (2.3 M in hexanes, 2.14 mL, 4.92 mmol) in THF (25 mL) at −78° C. After stirring for 15 minutes, a solution of 4-bromo-6,7-difluoroquinoline (1.20 g, 4.92 mmol) in THF (25 mL) was added slowly via cannula. After stirring an additional 1.5 hours, chlorotrimethylsilane (0.690 mL, 5.40 mmol) was added dropwise. After stirring one additional hour, the solution was poured into saturated NH4Cl (aq) (100 mL) then diluted with water (100 mL) and EtOAc (200 mL). The organic layer was separated, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography eluting with 0-10% EtOAc/hexanes to afford the title compound as a light yellow solid: 1H NMR (500 MHz, CDCl3): δ 8.60 (d, J=4.7 Hz, 1H); 7.93 (dd, J=10.8, 8.6 Hz, 1H); 7.64 (d, J=4.7 Hz, 1H); 0.49 (s, 9H); LC4: 2.86 min. (M+H) 316.

Workup

  1. stirringAfter stirring an additional 1.5 hours
  2. stirringAfter stirring one additional hour
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 0-10% EtOAc/hexanes

Sources & evidence

ORD record
ord-608f2763f6174f36a217d85fe8b3211a
Source dataset
uspto-grants-2013_05
Patent number
US08436015B2

Reaction notes

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