Chlorotrimethylsilane → HCID 11851783, compound

HRID 1864765Notes

Reaction equation

HRID 1864765 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][C@:13]2([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:17]([C:18](=[O:20])[CH3:19])[N:16]=[C:15]([C:21]3[CH:26]=[C:25](Br)[CH:24]=[CH:23][C:22]=3[F:28])[CH2:14]2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[Li]CCCC.Cl[Si:41]([CH3:44])([CH3:43])[CH3:42]>C1COCC1>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][C@:13]2([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:17]([C:18](=[O:20])[CH3:19])[N:16]=[C:15]([C:21]3[CH:26]=[C:25]([Si:41]([CH3:44])([CH3:43])[CH3:42])[CH:24]=[CH:23][C:22]=3[F:28])[CH2:14]2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 69021862HCID 69021862, compoundHCID 178418339Butyllithium

Product 1

HCID 11851783HCID 11851783, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 53 mg (0.100 mmol) 3-7 in 0.75 mL anhydrous THF at −78° C. under N2 was added 60 μL (0.150 mmol) 2.5 M n-BuLi in hexanes dropwise. Immediately following this addition, 51 μL (0.400 mmol) chlorotrimethylsilane was added, the cooling bath was removed, and the reaction warmed to room temperature. After 30 min the reaction was quenched with saturated aqueous NH4Cl solution and partitioned between EtOAc and saturated aqueous NaHCO3 solution. The organic phase was washed with water, brine, dried with Na2SO4 and concentrated. The residue was purified by reverse-phase preparatory HPLC with CH3CN/H2O (with 0.1% TFA). The fractions containing the desired product were poured into saturated aqueous NaHCO3 solution and extracted with EtOAc and concentrated to yield the freebase 3-8 as a clear, colorless oil.

Workup

  1. additionwas added
  2. customthe cooling bath was removed
  3. customAfter 30 min the reaction was quenched with saturated aqueous NH4Cl solution
  4. custompartitioned between EtOAc and saturated aqueous NaHCO3 solution
  5. washThe organic phase was washed with water, brine
  6. dry with materialdried with Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by reverse-phase preparatory HPLC with CH3CN/H2O (with 0.1% TFA)
  9. additionThe fractions containing the desired product
  10. additionwere poured into saturated aqueous NaHCO3 solution
  11. extractionextracted with EtOAc
  12. concentrationconcentrated
  13. customto yield the freebase 3-8 as a clear, colorless oil

Sources & evidence

ORD record
ord-0ef431f2a4ba4c4584399324a714532a
Source dataset
uspto-grants-2009_12
Patent number
US07625936B2

Reaction notes

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