Hydrochloric Acid → Ethyl (4-fluoronaphthalen-1-yl)(oxo)acetate

HRID 1060218Notes

Reaction equation

HRID 1060218 reaction equation
C([Li])CCC.Br[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([F:17])=[CH:9][CH:8]=1.[C:18](OCC)(=[O:24])[C:19]([O:21][CH2:22][CH3:23])=[O:20].Cl>C1COCC1.O.CCOC(C)=O>[F:17][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7]([C:18](=[O:24])[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7268Diethyl OxalateHCID 676471-Bromo 4-fluoronaphthaleneHCID 178418339Butyllithium

Product 1

HCID 22475340Ethyl (4-fluoronaphthalen-1-yl)(oxo)acetateYield 76.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of n-butyllithium (2.5 M in THF, 20 mL, 50 mmol) was cooled to −78° C., and a solution of 1-bromo-4-fluoronaphthalene (11.25 g, 50 mmol) in THF (40 mL) was added slowly and the mixture was stirred for 1 hour. The reaction mixture was warmed to −20° C., then added to a solution of diethyl oxalate (29.2 g,200 mmol) in THF (40 mL) at −78° C. After slowly warming-up to room temperature, EtOAc (100 mL), 10% HCl (50 mL) and water (50 mL) were added and the phases were separated. The aqueous layer was extracted with EtOAc (2×100 mL), and the organic layers were combined, washed with brine (50 mL), and dried over Na2SO4. After evaporating the solvent and the excess diethyl oxalate under high vacuum, the residue was purified by flash column chromatography (1:1 DCM:hexane) to give the title compound (9.4 g, 76% yield) as a white solid. 1H-NMR (400 MHz, CDCl3) δ (9.13 (d, J=8.6 Hz, 1H), 8.20 (d, J=8.4 Hz, 1H), 8.01 (dd, J=8.2, 5.4 Hz, 1H), 7.76 (t, J=7.2 Hz, 1H), 7.67 (t, J=8.1 Hz, 1H), 7.21 (t, J=8.5 Hz, 1H), 4.49 (q, J=7.1 Hz, 2H), 1.45 (t, J=7.1 Hz, 3H).

Workup

  1. temperatureAfter slowly warming-up to room temperature
  2. customthe phases were separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×100 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. customAfter evaporating the solvent
  7. customthe excess diethyl oxalate under high vacuum, the residue was purified by flash column chromatography (1:1 DCM:hexane)

Sources & evidence

ORD record
ord-066e32797f8f41c6b3a80e8316f56b5b
Source dataset
uspto-grants-2003_02
Patent number
US06521663B2

Reaction notes

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