Chlorotrimethylsilane → HCID 25234411, compound

HRID 1675504Notes

Reaction equation

HRID 1675504 reaction equation
[Si](Cl)(C)(C)C.BrCCBr.Br[C:11]1[S:12][CH:13]=[CH:14][N:15]=1.Br[C:17]1[CH2:22][CH2:21][CH2:20][C:19](=[O:23])[CH:18]=1.[Cl-].[NH4+]>[Zn].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.CN(C)C(=O)C>[S:12]1[CH:13]=[CH:14][N:15]=[C:11]1[C:17]1[CH2:22][CH2:21][CH2:20][C:19](=[O:23])[CH:18]=1

Participants

10

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 25517Ammonium ChlorideHCID 764302-BromothiazoleHCID 109650383-Bromocyclohex-2-enone

Product 1

HCID 25234411HCID 25234411, compoundYield 28%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalyst2×HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

To a 100 mL round bottom flask containing a stir bar was added 0.185 g of zinc dust (2.83 mmol) and 3 mL of N,N-dimethylacetamide. The flask was placed under nitrogen and 0.08 mL of TMS-chloride (0.63 mmol) and 0.05 mL of 1,2-dibromoethane (0.58 mmol) were added by syringe. The reaction was stirred for 5 min. and 0.09 mL of 2-bromothiazole (0.998 mmol) was added by syringe. The reaction was stirred for 1 hour at room temperature under nitrogen. To a separate 100 mL round bottom flask containing a stir bar was added 0.124 g of 3-bromocyclohex-2-enone (0.708 mmol) and 0.024 g of Pd(PPh3)2Cl2 (4.8 mol %), and 10 mL of anhydrous THF. The previously prepared organozinc species was added to the enone solution dropwise with removal of excess zinc using a syringe fitted with a cotton plug. The reaction was heated overnight at 60° C. in an oil bath with stirring under nitrogen atmosphere. The reaction was worked up by transferring the solution to a vial containing 10 mL of saturated ammonium chloride solution, and the product was extracted with ethyl acetate (2 times with 8 mL). The organic layer was dried with sodium sulfate, filtered, and solvent was concentrated under reduced pressure. The product was purified by flash chromatography using the Biotage system utilizing gradient elution (0% to 80% ethyl acetate/hexanes). Product fractions were combined and concentrated to yield a pale yellow solid (35 mg, 28%). 1H NMR (CDCl3, 300 MHz): δ 2.17 (quintet, J=6.3 Hz, 2H), 2.52 (t, J=6.3 Hz, 2H), 2.97 (td, J=6.3, 1.5 Hz, 2H), 6.69 (br s, 1H), 7.45 (d, J=3.0 Hz, 1H), 7.93 (d, J=3.0 Hz, 1H). 13C NMR (CDCl3, 75 MHz): δ 22.4, 27.0, 37.8, 121.4, 126.6, 144.4, 151.7, 166.7, 199.4. LCMS (ESI): mass calcd for (C9H9NOS) m/z 179.04; measured [M+H]+: m/z 180.03.

Workup

  1. additionTo a 100 mL round bottom flask containing a stir bar
  2. stirringThe reaction was stirred for 1 hour at room temperature under nitrogen
  3. additionTo a separate 100 mL round bottom flask containing a stir bar
  4. customfitted with a cotton plug
  5. stirringwith stirring under nitrogen atmosphere
  6. extractionthe product was extracted with ethyl acetate (2 times with 8 mL)
  7. dry with materialThe organic layer was dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationsolvent was concentrated under reduced pressure
  10. customThe product was purified by flash chromatography
  11. washthe Biotage system utilizing gradient elution (0% to 80% ethyl acetate/hexanes)
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-888e6940c3c14147a80fba472da89918
Source dataset
uspto-grants-2011_08
Patent number
US08003692B2

Reaction notes

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