Diethyl Oxalate → Ethyl 4-fluoro-2-methyl-α-oxobenzeneacetate

HRID 599266Notes

Reaction equation

HRID 599266 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[CH3:14].[C:15](OCC)(=[O:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17]>C1COCC1>[F:13][C:10]1[CH:11]=[CH:12][C:7]([C:15](=[O:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:8]([CH3:14])[CH:9]=1

Participants

5

Reactant 3

HCID 7268Diethyl OxalateHCID 967432-Bromo-5-fluorotolueneHCID 178418339Butyllithium

Product 1

HCID 24722272Ethyl 4-fluoro-2-methyl-α-oxobenzeneacetateYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (1.6 M in hexane, 109 mL, 0.175 mol) was added dropwise to a −78° C. solution of 1-bromo-4-fluoro-2-methylbenzene (30 g, 0.16 mol) in THF (500 mL) under N2. After complete addition, the reaction mixture was stirred for 1 h at −78° C. The bright yellow solution was quickly cannulated to another flask containing a pre-cooled (−78° C.) solution of diethyl oxalate (27.8 g, 0.19 mol) in THF (400 mL). After stirring for another 30 min at −78° C., the reaction mixture was quenched by the addition of saturated NH4Cl solution (800 mL). The aqueous layer was extracted with EtOAc (3×400 mL) and the combined organics were dried (Na2SO4), concentrated in vacuo and purified via silica gel chromatography to provide ethyl 2-(4-fluoro-2-methylphenyl)-2-oxoacetate (22.0 g, yield, 66% yield). 1H NMR (400 MHz, CDCl3): δ 7.73 (dd, J=9.2, 5.6 Hz, 1 H), 7.02-6.96 (m, 2 H), 4.40 (m, 2 H), 2.60 (s, 3 H), 1.29 (t, J=6.8 Hz, 3 H). MS (ESI) m/z: 233.0 [M+Na]+

Workup

  1. additionAfter complete addition
  2. customThe bright yellow solution was quickly cannulated to another flask
  3. additioncontaining
  4. stirringAfter stirring for another 30 min at −78° C.
  5. customthe reaction mixture was quenched by the addition of saturated NH4Cl solution (800 mL)
  6. extractionThe aqueous layer was extracted with EtOAc (3×400 mL)
  7. dry with materialthe combined organics were dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. custompurified via silica gel chromatography

Sources & evidence

ORD record
ord-965c94ac89574d0b97e4954c7ae99980
Source dataset
uspto-grants-2011_03
Patent number
US07897762B2

Reaction notes

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