tert-Butyl acetate → Tert-butyl 2-(2-chloro-5-isopropyl-phenyl)acetate

HRID 1854582Notes

Reaction equation

HRID 1854582 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[C:12]1[CH:17]=[C:16]([CH:18]([CH3:20])[CH3:19])[CH:15]=[CH:14][C:13]=1[Cl:21].[C:22]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])(=[O:24])[CH3:23].[Cl-].[NH4+]>C(OCC)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C1(C)C=CC=CC=1>[Cl:21][C:13]1[CH:14]=[CH:15][C:16]([CH:18]([CH3:20])[CH3:19])=[CH:17][C:12]=1[CH2:23][C:22]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]

Participants

9

Reactant 4

HCID 10908tert-Butyl acetateHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 509978643-Bromo-4-chloroisopropylbenzene

Product 1

HCID 117720579Tert-butyl 2-(2-chloro-5-isopropyl-phenyl)acetateYield 90.4%

Reagents, catalysts & solvents 4

HCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

Add bis(dibenzylideneacetone)palladium (49.2 mg, 85.6 μmol) to a round bottom flask and seal with a septum. Flush with nitrogen. Add tri-tert-butylphosphine (85.6 μL, 85.6 μmol, 1M in toluene) and lithium bis(trimethylsilyl)amide (12.8 mL, 11.56 mmol, 0.9M in methylcyclohexanes) via a syringe. Add 2-bromo-1-chloro-4-isopropyl-benzene (1.0 g, 4.28 mmol) and t-butyl acetate (865.2 μL, 6.42 mmol) via a syringe. Add toluene (10.7 mL) via a syringe and the reaction mixture becomes hot to the touch. Place on an ambient temperature water bath and stir for 3 hours. Store the reaction mixture in the freezer over the weekend. Warm the reaction mixture to ambient temperature. Dilute the reaction mixture with diethyl ether and add saturated ammonium chloride solution. Separate the layers and wash the diethyl ether layer with saturated sodium chloride solution. Dry over sodium sulfate, filter and concentrate under reduced pressure. Purify the residue by silica gel chromatography eluting with acetone: hexanes (0-2% gradient) to give the title compound (1.04 g). Purify again by silica gel chromatography eluting with dichloromethane: hexanes (0-20% gradient) to give the title compound (490 mg, 1.82 mmol). MS (m/z): 213.0 (M-tBu+1).

Workup

  1. customseal with a septum
  2. customFlush with nitrogen
  3. customPlace on an ambient temperature
  4. customSeparate the layers
  5. washwash the diethyl ether layer with saturated sodium chloride solution
  6. dry with materialDry over sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify the residue by silica gel chromatography
  10. washeluting with acetone

Sources & evidence

ORD record
ord-4f15eebe23404caf92548f6ab4a0f95c
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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