2-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylacetamide → 2-(Tert-butyldimethylsilyloxy)-1-(3-chloro-4-fluorophenyl)ethanone

HRID 1774151Notes

Reaction equation

HRID 1774151 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[CH:6][C:7]=1[F:8].[Si:11]([O:18][CH2:19][C:20](N(OC)C)=[O:21])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]>C1COCC1.CCCCCC>[Si:11]([O:18][CH2:19][C:20]([C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1)=[O:21])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]

Participants

5

Reactant 2

HCID 116010942-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylacetamideHCID 178505834HCID 178505834, compound

Product 1

HCID 866966542-(Tert-butyldimethylsilyloxy)-1-(3-chloro-4-fluorophenyl)ethanoneYield 87.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

0.5M (3-Chloro-4-fluorophenyl)magnesium bromide in THF (27.4 mL, 13.7 mmol) was added dropwise to 2-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylacetamide (2.00 g, 8.57 mmol) in THF (20 mL) cooled in ice. The mixture became turbid after about half of the Grignard reagent was added. This was stirred in an ice bath for 2 hours, quenched with saturated aqueous NH4Cl, and concentrated to remove the THF. The aqueous residue was extracted with 2 portions DCM. The combined DCM layers were dried over MgSO4, filtered, and evaporated to yield a crude product (3.62 g) as an oil. This was taken up in hexane and purified on a silica gel plug with hexane until product started eluting, then 15:1 hexane/EtOAc. Product-containing fractions yielded 2-(tert-butyldimethylsilyloxy)-1-(3-chloro-4-fluorophenyl)ethanone (2.28 g, 7.53 mmol, 87.9% yield) as an oil.

Workup

  1. temperaturecooled in ice
  2. additionwas added
  3. customquenched with saturated aqueous NH4Cl
  4. concentrationconcentrated
  5. customto remove the THF
  6. extractionThe aqueous residue was extracted with 2 portions DCM
  7. dry with materialThe combined DCM layers were dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto yield a crude product (3.62 g) as an oil
  11. custompurified on a silica gel plug with hexane until product
  12. washstarted eluting

Sources & evidence

ORD record
ord-421d8eb7c8e745698f13ccfedef639f3
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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