Hydrochloric Acid → Clobuzarit

HRID 1702544Notes

Reaction equation

HRID 1702544 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.O[C:17]([CH3:22])([CH3:21])[C:18]([OH:20])=[O:19].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([Mg]Cl)(C)(C)C.[Mg].C(Cl)(C)(C)C.Cl>ClC1C=CC=CC=1.CCOCC.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:15]=[CH:14][C:11]([CH2:12][O:13][C:17]([CH3:22])([CH3:21])[C:18]([OH:20])=[O:19])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 10486tert-BUTYL CHLORIDEHCID 116712-Hydroxyisobutyric acidHCID 521998p-Toluenesulfonic acid monohydrateHCID 5925704'-Chloro[1,1'-biphenyl]-4-carbaldehydeHCID 5462224MagnesiumHCID 178418310HCID 178418310, compound

Product 1

HCID 71697ClobuzaritYield 15.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 7964ChlorobenzeneSolvent

Procedure

A solution of 4-(4-chlorophenyl)benzaldehyde (41.5 g.) in chlorobenzene (250 ml.) containing in addition 2-hydroxy-2-methylpropionic acid (29.7 g.) and p-toluenesulphonic acid monohydrate (2.7 g.) was heated under reflux for 6 hours at reduced pressure (105° C., 313 mm Hg) with continuous removal of water by azeotropic distillation. The solution was then cooled, washed successively with 10% w/v sodium carbonate solution (500 ml.) and water (2×500 ml.), dried (MgSO4), filtered and diluted with fresh chlorobenzene to a volume of 350 ml. to give a solution containing 14.3% w/v of 2-[4-(4-chlorophenyl)-phenyl]-5,5-dimethyl-1,3-dioxolanone-4-one, as estimated by gas-liquid chromatography. This solution (35 ml.) was added during 1 hour at 0° to 5° C. under an argon atmosphere to a stirred solution of t-butyl magnesium chloride [prepared from magnesium turnings (1.61 g.) and a solution of t-butyl chloride (9.33 ml.) in anhydrous ether (40 ml.)]. The mixture was stirred for 1 hour at 0° to 5° C. and then for a further 16 hours at room temperature before being poured into 1.5 M hydrochloric acid (100 ml.). The organic phase was separated and washed with water (2×100 ml.), dried (Na2SO4) and evaporated to give 2-[4-(4-chlorophenyl)benzyloxy]-2-methyl-propionic acid (9.23 g.), m.p. 154°-155° C., after recrystallisation from toluene.

Workup

  1. temperaturewas heated
  2. temperatureThe solution was then cooled
  3. washwashed successively with 10% w/v sodium carbonate solution (500 ml.) and water (2×500 ml.)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. additiondiluted with fresh chlorobenzene to a volume of 350 ml
  7. customto give a solution
  8. additioncontaining 14.3%
  9. customThe organic phase was separated
  10. washwashed with water (2×100 ml.)
  11. dry with materialdried (Na2SO4)
  12. customevaporated

Sources & evidence

ORD record
ord-be3f59e8cfda4c3390c659c9dcb9b685
Source dataset
uspto-grants-1982_09
Patent number
US04348322

Reaction notes

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