Hydrochloric Acid → 4-Chloro-3-fluoro-2-methylsulphenylbenzoic acid

HRID 2393025Notes

Reaction equation

HRID 2393025 reaction equation
C([Li])CCC.[Cl:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][C:8]=1[F:16].[CH3:17][S:18]SC.Cl>O1CCCC1>[Cl:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[C:9]([S:18][CH3:17])[C:8]=1[F:16]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 12232Dimethyl DisulfideHCID 27365364-Chloro-3-fluorobenzoic acidHCID 178418339Butyllithium

Product 1

HCID 152187374-Chloro-3-fluoro-2-methylsulphenylbenzoic acidYield 69.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-Butyl lithium (2.5M in hexane; 180 ml) was added with cooling to a solution of 4-chloro-3-fluorobenzoic acid (37.5 g) in dry tetrahydrofuran while maintaining the temperature below -40° C. The mixture was stirred at -30° to -40° C. for 3 hours. Dimethyl disulphide (60.5 g) was added and the mixture was stirred at -40° C. for 0.5 hours and at room temperature overnight. Hydrochloric acid (2M) was added and the layers were separated. The aqueous layer was extracted with ether and the combined organic layers were extracted with aqueous sodium hydroxide (2M) and water. The aqueous extracts were combined and acidified to pH 1 and extracted with ether, washed with water, dried (Na2 SO4) and filtered. The filtrate was evaporated to dryness and the residue was triturated with n-hexane and filtered to give 4-chloro-3-fluoro-2-methylsulphenylbenzoic acid (32.84 g) as a yellow solid, m.p. 149.5°-150.5° C.

Workup

  1. temperaturewhile maintaining the temperature below -40° C
  2. stirringthe mixture was stirred at -40° C. for 0.5 hours and at room temperature overnight
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with ether
  5. extractionthe combined organic layers were extracted with aqueous sodium hydroxide (2M) and water
  6. extractionextracted with ether
  7. washwashed with water
  8. customdried (Na2 SO4)
  9. filtrationfiltered
  10. customThe filtrate was evaporated to dryness
  11. customthe residue was triturated with n-hexane
  12. filtrationfiltered

Sources & evidence

ORD record
ord-c2acc01748cb4ac9a7f8c3040ddc5e78
Source dataset
uspto-grants-1998_09
Patent number
US05804532

Reaction notes

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