Hydrochloric Acid → 4-Benzoyl-3-(methylsulfanyl)-1,3-dihydro-2H-indol-2-one

HRID 442537Notes

Reaction equation

HRID 442537 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:6].C(OCl)(C)(C)C.[CH3:22][S:23][CH2:24][C:25](OCC)=[O:26].C(N(CC)CC)C.Cl>C(Cl)Cl>[C:5]([C:4]1[CH:13]=[CH:14][CH:15]=[C:2]2[C:3]=1[CH:24]([S:23][CH3:22])[C:25](=[O:26])[NH:1]2)(=[O:6])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 17817Methanone, (3-aminophenyl)phenyl-HCID 78199Ethyl (methylthio)acetateHCID 521297Tert-Butyl hypochlorite

Product 1

HCID 129235524-Benzoyl-3-(methylsulfanyl)-1,3-dihydro-2H-indol-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

A solution of 30.6 (0.152 mole) of 3-aminobenzophenone in 160 ml. of methylene chloride was cooled to -78° C. in a dry ice/acetone bath and treated dropwise under a nitrogen atmosphere with a solution of 16.5 g. (0.152 mole) of t-butylhypochlorite in 60 ml. of methylene chloride. After stirring for 1 hr. after addition was comlete, thin layer chromatography showed no starting material. A solution of 20.2 g. (0.152 mole) of ethyl α-(methylthio)acetate in 60 ml. of methylene chloride was added dropwise and stirring continued at -78° C. for 2.5 hr. A solution of 15.4 g. (0.152 mole) of triethylamine in 60 ml. of methylene chloride was added dropwise at -78° C. and the reaction mixture allowed to warm to room temperature while stirring for 16 hr. (overnight). The dark brown solution was treated with 100 ml. of 3N hydrochloric acid and stirred for 3 hrs. at room temperature. Precipitation of a tan solid began after 15-30 minutes. Filtration gave 18.5 g. of solid, m.p. 224°-228° C. (dec.) The layers of the filtrate were separated, the organic phase dried over magnesium sulfate, evaporated under reduced pressure, and the residue triturated in isopropyl ether (25 g.). The gummy solid was triturated in cold methanol to give 8.3 g. of product, m.p. 222°-225° C. (dec.). The total yield was 26.8 g. (62%). A 7.0 g. sample recrystallized from methanol weighed 5.6 g. and melted at 235°-237° C. (dec.).

Workup

  1. additiontreated dropwise under a nitrogen atmosphere with a solution of 16.5 g
  2. additionafter addition
  3. stirringstirring
  4. waitcontinued at -78° C. for 2.5 hr
  5. stirringwhile stirring for 16 hr
  6. custom(overnight)
  7. additionThe dark brown solution was treated with 100 ml
  8. customat room temperature
  9. customPrecipitation of a tan solid
  10. waitbegan after 15-30 minutes
  11. filtrationFiltration
  12. customgave 18.5 g
  13. customof solid, m.p. 224°-228° C. (dec.) The layers of the filtrate were separated
  14. dry with materialthe organic phase dried over magnesium sulfate
  15. customevaporated under reduced pressure
  16. customthe residue triturated in isopropyl ether (25 g.)
  17. customThe gummy solid was triturated in cold methanol
  18. customto give 8.3 g
  19. customsample recrystallized from methanol

Sources & evidence

ORD record
ord-71e2a1dadf57464eb3ab826c81cbe5bc
Source dataset
uspto-grants-1977_08
Patent number
US04045576

Reaction notes

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