4-Bromothioanisole → 2-Trimethylsilyloxy-4'-(methylthio)isobutyrophenone

HRID 1019185Notes

Reaction equation

HRID 1019185 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][CH:3]=1.[Li]CCCC.[CH3:15][Si:16]([CH3:26])([CH3:25])[O:17][C:18]([CH3:24])([CH3:23])[C:19](OC)=[O:20]>C1COCC1.CCCCCC>[CH3:15][Si:16]([CH3:26])([CH3:25])[O:17][C:18]([CH3:24])([CH3:23])[C:19]([C:2]1[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][CH:3]=1)=[O:20]

Participants

6

Reactant 3

HCID 660374-BromothioanisoleHCID 14297555Methyl 2-methyl-2-[(trimethylsilyl)oxy]propanoateHCID 178418339Butyllithium

Product 1

HCID 184001902-Trimethylsilyloxy-4'-(methylthio)isobutyrophenoneYield 33.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 204 mg (1.0 mmol) of 4-bromothioanisole in 2.5 mL of THF was cooled to −78° C. and treated with 0.42 mL of 2.5 M n-BuLi solution in hexane. After stirring at −78° C. for 1 h, a solution of 380 mg (2.0 mmol) of methyl 2-trimethylsilyloxyisobutyrate in 2 mL of THF was added. The mixture was stirred at −78° C. for 2 h and then quenched with NH4OAc buffer. The product was extracted with EtOAc, dried over MgSO4 and concentrated. The residue was purified by flash chromatography, eluting with 19:1 hexane/EtOAc to give 95 mg of the title product. 1H NMR (CD3COCD3) d 0.05 (9H, s), 1.52 (6H, s), 2.53 (3H, s), 7.33 (2H, d), 8.12 (2H, d).

Workup

  1. stirringThe mixture was stirred at −78° C. for 2 h
  2. customquenched with NH4OAc buffer
  3. extractionThe product was extracted with EtOAc
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography
  7. washeluting with 19:1 hexane/EtOAc

Sources & evidence

ORD record
ord-2f1474bc66c648238c2a3db68ca10966
Source dataset
uspto-grants-2002_11
Patent number
US06486194B2

Reaction notes

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