Ammonia → HCID 13922820, compound

HRID 2232337Notes

Reaction equation

HRID 2232337 reaction equation
C(OC([O:7][CH2:8]C)CBr)C.[CH3:10][O:11][C:12]1[CH:13]=[C:14](S)[CH:15]=[CH:16][CH:17]=1.C(OC(OCC)C[S:24][C:25]1[CH:30]=CC=C(OC)C=1)C.C([Li])CCC.[S:41](=[O:43])=[O:42].[NH3:44]>O1CCCC1.CC(C)=O>[OH:7][CH2:8][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]2[S:24][C:25]([S:41](=[O:43])(=[O:42])[NH2:44])=[CH:30][C:14]=2[CH:13]=1

Participants

9

Reactant 6

HCID 222AmmoniaHCID 1119Sulfur DioxideHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 849893-MethoxybenzenethiolHCID 13642516(2,2-Diethoxyethyl)(3-methoxyphenyl)sulfaneHCID 178418339Butyllithium

Product 1

HCID 13922820HCID 13922820, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent

Procedure

6-Methoxy-2-sulfamoylbenzo[b]thiophene, a novel compound and a key intermediate for many of the other novel compounds of this invention, is obtained by reacting bromoacetaldehyde diethyl acetal in the presence of a base with at least a molar equivalent of m-methoxybenzenethiol in a suitable inert solvent, preferably acetone, at a temperature extending to reflux. After reaction is essentially complete the 1-[(2,2-diethoxy)ethylthio]-3-methoxybenzene obtained is collected and suitably extracted, washed and dried. The dried product is then slowly added to at least a molar equivalent of the catalyst boron trifluoride.etherate in an inert solvent such as chloroform at a temperature extending to reflux until reaction is essentially completed. Preferably the reaction is conducted under an inert atmosphere such as nitrogen. A mixture of 6-methoxybenzo[b]thiophene and 4-methoxybenzo[b]thiophene in an approximate ratio of 10:1 is obtained upon evaporation of the solvent. The mixture is treated with at least a molar equivalent of n-butyl lithium in an inert solvent such as tetrahydrofuran at a reduced temperature, preferably below -10° C., most suitably at -70° C. Sulfur dioxide gas is then passed over the solution at a rate such that the reaction mixture does not exceed a temperature of -10° C. After the reaction is complete, the solvents are removed and the product reacted with at least one molar equivalent of N-chlorosuccinimide at reduced temperature, generally 0° C. or less. The mixture of 4- and 6-methoxybenzo[b]thiophene-2-sulfonyl chlorides that is produced is treated with concentrated aqueous ammonia. The resulting mixture of 4- and 6-methoxy-2-sulfamoylbenzo[b]thiophenes is then collected and the isomers are separated by fractional crystallization. Each is further purified by reprecipitation from aqeuous base by treatment with acid and/or recrystallization from an appropriate solvent.

Workup

  1. temperatureto reflux
  2. customAfter reaction
  3. customobtained
  4. customis collected
  5. extractionsuitably extracted
  6. washwashed
  7. customdried
  8. additionThe dried product is then slowly added to at least a molar equivalent of the catalyst boron trifluoride
  9. temperatureto reflux until reaction
  10. additionA mixture of 6-methoxybenzo[b]thiophene and 4-methoxybenzo[b]thiophene in an approximate ratio of 10:1
  11. customis obtained upon evaporation of the solvent
  12. custommost suitably at -70° C
  13. customa temperature of -10° C
  14. customthe solvents are removed
  15. customthe product reacted with at least one molar equivalent of N-chlorosuccinimide at reduced temperature, generally 0° C. or less
  16. customis produced
  17. customis then collected
  18. customthe isomers are separated by fractional crystallization
  19. customEach is further purified by reprecipitation from aqeuous base by treatment with acid and/or recrystallization from an appropriate solvent

Sources & evidence

ORD record
ord-079a7afdfc9b4f62b37bcbdcb94d2481
Source dataset
uspto-grants-1988_11
Patent number
US04788192

Reaction notes

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