Sodium Hydroxide → 2-[3-Chloro-4-(pyrazol-1-yl)phenyl]propionic acid

HRID 1732995Notes

Reaction equation

HRID 1732995 reaction equation
NC1C=CC(C(C)C(O)=O)=CC=1Cl.N([O-])=O.[Na+].S([O-])(O)=O.[Na+].ClC1C=C(C(C)C(O)=O)C=CC=1NN.C(OC(OCC)CC(OCC)OCC)C.[OH-].[Na+].C([O:56][C:57](=[O:72])[CH:58]([C:60]1[CH:65]=[CH:64][C:63]([N:66]2[CH:70]=[CH:69][CH:68]=[N:67]2)=[C:62]([Cl:71])[CH:61]=1)[CH3:59])C>Cl.O>[Cl:71][C:62]1[CH:61]=[C:60]([CH:58]([CH3:59])[C:57]([OH:72])=[O:56])[CH:65]=[CH:64][C:63]=1[N:66]1[CH:70]=[CH:69][CH:68]=[N:67]1

Participants

10

Reactant 7

HCID 14798Sodium HydroxideHCID 671471,1,3,3-TetraethoxypropaneHCID 130652322-(4-Amino-3-chlorophenyl)propanoic acidHCID 203035302-(3-Chloro-4-hydrazinophenyl)propionic acidHCID 23665763Sodium BisulfiteHCID 23668193Sodium NitriteHCID 545042332-[3-Chloro-4-(pyrazol-1-yl)phenyl]propionic acid ethyl ester

Product 1

HCID 203035002-[3-Chloro-4-(pyrazol-1-yl)phenyl]propionic acidYield 96%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

20 g (100 mmoles) of 2-(4-amino-3-chlorophenyl) propionic acid are dissolved in 20 ml of concentrated hydrochloric acid and diazotized with 6.9 g of sodium nitrite in 20 ml of water at from -2° to -6° C. The solution is thereafter stirred for a further hour and subsequently stirred into 100 ml of a freshly-prepared, ice-cold, 5.5 N solution of sodium hydrogen sulfite. Heating is then effected slowly to a temperature of from 60° to 70° C. After one hour, acidification is effected with concentrated hydrochloric acid, and the resulting reaction mixture is left at 70° C. for a further 12 hours. 2-(3-chloro-4-hydrazinophenyl)propionic acid forms therein. 22 g (100 mmoles) of 1,1,3,3-tetraethoxypropane are then added thereto. After three hours' heating to 100° C., the reaction mixture is cooled, rendered alkaline with 35% strength sodium hydroxide solution and, in order to saponify the 2-[3-chloro-4-(pyrazol-1-yl)phenyl]propionic acid ethyl ester which is formed in addition to the acid, reheated for one hour. After cooling, impurities are extracted by shaking with benzene; the aqueous phase is acidified with concentrated hydrochloric acid; the product is extracted with diethyl ether; and the ether phase is washed with water, dried and concentrated in a vacuum. 24 g (96% of theory) of 2-[3-chloro-4-(pyrazol-1-yl)phenyl]propionic acid, m.p. 83° to 85° C., are thus obtained.

Workup

  1. temperatureHeating
  2. customis then effected slowly to a temperature of from 60° to 70° C
  3. customthe resulting reaction mixture
  4. waitis left at 70° C. for a further 12 hours
  5. temperaturethe reaction mixture is cooled
  6. customis formed in addition to the acid
  7. waitreheated for one hour
  8. temperatureAfter cooling
  9. extractionimpurities are extracted
  10. stirringby shaking with benzene
  11. extractionthe product is extracted with diethyl ether
  12. washand the ether phase is washed with water
  13. customdried
  14. concentrationconcentrated in a vacuum

Sources & evidence

ORD record
ord-a0fc8a13ca2b417a97874091f6941333
Source dataset
uspto-grants-1980_12
Patent number
US04239901

Reaction notes

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