2,3,4,5-Tetrafluorobenzoyl chloride → Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoate

HRID 1904603Notes

Reaction equation

HRID 1904603 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=O.C([Li])CCC.[F:15][C:16]1[C:24]([F:25])=[C:23]([F:26])[C:22]([F:27])=[CH:21][C:17]=1C(Cl)=O>O1CCCC1>[F:15][C:16]1[C:24]([F:25])=[C:23]([F:26])[C:22]([F:27])=[CH:21][C:17]=1[C:3]([CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6])=[O:5]

Participants

5

Reactant 3

HCID 27336892,3,4,5-Tetrafluorobenzoyl chlorideHCID 3595298Propanedioic acid, monoethyl esterHCID 178418339Butyllithium

Product 1

HCID 600916Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-36 °C

Procedure

In a nitrogen atmosphere a 50 gallon kettle was charged with 50.9 kg of tetrahydrofuran, 5.2 kg of monoethyl malonate and about 5 g of 2,2'-dipyridyl. After cooling the mixture to -36° C., 41.6 kg of n-butyllithium (15% in hexane) was added over 3 hours maintaining the temperature at -25° to -35° C. The resultant slurry was cooled further to -60° C. and then treated over about 50 minutes with the acid chloride of part (a) at -62° to -54° C. The green/yellow mixture was stirred for 2 hours at ambient temperature and allowed to warm further overnight. The mixture (-24° C.) was quenched (vacuum) into ambient dilute hydrochloric acid (15 L of muriatic acid and 61 L of deionized water). The quench mixture was separated and the organic phase was washed with 2×40 L of deionized water. The combined aqueous phases were back extracted with 40 L of hexane-ether (1:1). All organic layers were combined and washed with 100 L of saturated sodium bicarbonate solution; again back extracting the aqueous phase with 40 L of hexane-ether (1:1). The combined organic layers were concentrated to an oil in vacuo followed by dissolution in 20 L of hexane and repeated concentration to dryness. The hot oil was finally dissolved in 19 L of hexane. The solution was cooled to -5° C. and the crystallized solids were filtered using 4.8 L of cold (-6° C.) hexane as wash. The material was dried in vacuo at room temperature affording 4234 g of product suitable for use in the next step. A second crop was obtained by concentrating the combined filtrate and wash and cooling to low temperature. The combined yield for the first and second crops was 4841 g (74.9%).

Workup

  1. temperaturemaintaining the temperature at -25° to -35° C
  2. temperatureThe resultant slurry was cooled further to -60° C.
  3. temperatureto warm further overnight
  4. customThe mixture (-24° C.) was quenched (vacuum) into ambient dilute hydrochloric acid (15 L of muriatic acid and 61 L of deionized water)
  5. customThe quench mixture was separated
  6. washthe organic phase was washed with 2×40 L of deionized water
  7. extractionThe combined aqueous phases were back extracted with 40 L of hexane-ether (1:1)
  8. washwashed with 100 L of saturated sodium bicarbonate solution
  9. extractionagain back extracting the aqueous phase with 40 L of hexane-ether (1:1)
  10. concentrationThe combined organic layers were concentrated to an oil in vacuo
  11. dissolutionfollowed by dissolution in 20 L of hexane
  12. concentrationconcentration to dryness
  13. dissolutionThe hot oil was finally dissolved in 19 L of hexane
  14. temperatureThe solution was cooled to -5° C.
  15. filtrationthe crystallized solids were filtered
  16. custom4.8 L of cold (-6° C.) hexane
  17. washas wash
  18. customThe material was dried in vacuo at room temperature

Sources & evidence

ORD record
ord-fb8b962002f649af8026a04947db967b
Source dataset
uspto-grants-1989_06
Patent number
US04839355

Reaction notes

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