Hydrochloric Acid → HCID 18663598, compound

HRID 1956596Notes

Reaction equation

HRID 1956596 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:3]=1[CH2:15][C:16]#N.C([O:20][C:21](=[O:27])C(OCC)=O)C.C([O-])C.[Na+].[Na].Cl.S(=O)(=O)(O)O>C(O)(=O)C.O>[Cl:1][C:2]1[C:3]2[CH:15]=[C:16]([C:21]([OH:27])=[O:20])[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[O:8][C:4]=2[CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 7268Diethyl OxalateHCID 2723922Sodium ethoxideHCID 5360545SodiumHCID 22378378HCID 22378378, compound

Product 1

HCID 18663598HCID 18663598, compoundYield 60.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

10.82 g (44.40 mmol) of (2-chloro-6-phenoxy-phenyl)-acetonitrile and 7.85 g (53.72 mmol) of oxalic acid diethyl ester are added at room temperature to a freshly prepared sodium ethanolate solution (1.5 g (53.72 mmol) of sodium in 50 ml of ethanol) and the mixture is stirred for 18 hours. The mixture is rendered acidic with 1N hydrochloric acid, concentrated using a rotary evaporator and extracted 2× with ethyl acetate, and the organic phase is washed with brine, dried over sodium sulfate and concentrated to yield 15.99 g of crude intermediate (3-(2-chloro-6-phenoxy-phenyl)-2-hydroxy-4-nitrilo-but-2-enoic acid ethyl ester). 15.0 g (approximately 43.6 mmol) of the above intermediate are placed in 105 ml of glacial acetic acid and stirred for 20 minutes, 51.9 ml of water and 51.9 ml of sulfuric acid are slowly added, and the mixture is heated for 4 hours under reflux and then for 18 hours at room temperature. The reaction mixture is extracted with ethyl acetate, the organic phase is washed with water and 3× with 4N sodium hydroxide, and the aqueous phase is extracted 1× with ethyl acetate. The aqueous phases are rendered acidic with concentrated hydrochloric acid and extracted 3× with ethyl acetate, and the organic phase is dried over sodium sulfate and concentrated. 7.71 g (28.27 mmol)=60.3% of 1-chloro-dibenz[b,f]oxepine-10-carboxylic acid are obtained in the form of a yellow solid; TLC (silica gel; ethyl acetate/hexane=1:1; UV): Rf =0.21; 1H-NMR (CDCl3, 200 MHz): 7.15-7.47 (m, 7H); 7.68 (m, 1H); 8.39 (s, 1H).

Workup

  1. concentrationconcentrated
  2. customa rotary evaporator
  3. extractionextracted 2× with ethyl acetate
  4. washthe organic phase is washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto yield 15.99 g of crude intermediate (3-(2-chloro-6-phenoxy-phenyl)-2-hydroxy-4-nitrilo-but-2-enoic acid ethyl ester)
  8. stirringstirred for 20 minutes
  9. temperaturethe mixture is heated for 4 hours
  10. temperatureunder reflux
  11. waitfor 18 hours at room temperature
  12. extractionThe reaction mixture is extracted with ethyl acetate
  13. washthe organic phase is washed with water and 3× with 4N sodium hydroxide
  14. extractionthe aqueous phase is extracted 1× with ethyl acetate
  15. extractionextracted 3× with ethyl acetate
  16. dry with materialthe organic phase is dried over sodium sulfate
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-562a303b126e47a7bd2eed918c6a7c60
Source dataset
uspto-grants-1998_07
Patent number
US05780501

Reaction notes

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