Hydrochloric Acid → 5-[5-(4-Chloro-phenyl)-2-oxo-6H-[1,3,4]oxadiazin-3-ylmethyl]-3-methylsulphanyl-1,3-dihydro-indol-2-one

HRID 1094011Notes

Reaction equation

HRID 1094011 reaction equation
[CH3:1][S:2][CH2:3][C:4](OCC)=[O:5].[NH2:9][C:10]1[CH:30]=[CH:29][C:13]([CH2:14][N:15]2[N:20]=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[CH2:18][O:17][C:16]2=[O:28])=[CH:12][CH:11]=1.C(OCl)(C)(C)C.C(N(CC)CC)C.Cl>C1COCC1>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([C:19]2[CH2:18][O:17][C:16](=[O:28])[N:15]([CH2:14][C:13]3[CH:29]=[C:30]4[C:10](=[CH:11][CH:12]=3)[NH:9][C:4](=[O:5])[CH:3]4[S:2][CH3:1])[N:20]=2)=[CH:22][CH:23]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 78199Ethyl (methylthio)acetateHCID 521297Tert-Butyl hypochloriteHCID 666364683-(4-Amino-benzyl)-5-(4-chloro-phenyl)-3,6-dihydro-[1,3,4]oxadiazin-2-one

Product 1

HCID 666362855-[5-(4-Chloro-phenyl)-2-oxo-6H-[1,3,4]oxadiazin-3-ylmethyl]-3-methylsulphanyl-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

Ethyl (methylsulphanyl)acetate (27.31 mmoles) is added dropwise to a solution of the compound obtained in Step E (23.75 mmoles) in THF (200 ml) at −60° C. under a nitrogen atmosphere. tBuOCl− (27.31 mmoles) is added dropwise to the reaction mixture over 20 minutes, keeping the temperature between −60° C. and −55° C. After stirring for 3 hours at −60° C., triethylamine (29.68 mmoles) is added dropwise. The reaction mixture is brought to ambient temperature; aqueous 3M HCl solution (340 ml) is then added and stirring is carried out for a further 2 hours. The organic phase is evaporated and the aqueous suspension is extracted with DCM. The organic phases are combined, then washed with 2M HCl solution and then with saturated NaCl solution, dried over sodium sulphate, filtered and evaporated to dryness. The residue is triturated in ethyl ether, filtered and dried in vacuo to yield the title product, which is used directly in the next Step.

Workup

  1. customthe temperature between −60° C. and −55° C
  2. customis brought to ambient temperature
  3. stirringstirring
  4. waitis carried out for a further 2 hours
  5. customThe organic phase is evaporated
  6. extractionthe aqueous suspension is extracted with DCM
  7. washwashed with 2M HCl solution
  8. dry with materialwith saturated NaCl solution, dried over sodium sulphate
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customThe residue is triturated in ethyl ether
  12. filtrationfiltered
  13. customdried in vacuo

Sources & evidence

ORD record
ord-63dcdf304e2143a9984a579b1bc4dab6
Source dataset
uspto-grants-2012_03
Patent number
US08133889B2

Reaction notes

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