Ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate → HCID 178469202, compound

HRID 1627891Notes

Reaction equation

HRID 1627891 reaction equation
[NH2:1][C:2]1[S:6][C:5]2[CH2:7][CH2:8][CH2:9][CH2:10][C:4]=2[C:3]=1[C:11]([O:13]CC)=O.[CH2:16]([O:18][C:19](=[O:26])[CH:20]=[C:21](OCC)[CH3:22])[CH3:17].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O-]CC.[Na+]>C1(C)C(C)=CC=CC=1.C(O)C.O>[CH2:16]([O:18][C:19]([C:20]1[C:11]([OH:13])=[C:3]2[C:4]3[CH2:10][CH2:9][CH2:8][CH2:7][C:5]=3[S:6][C:2]2=[N:1][C:21]=1[CH3:22])=[O:26])[CH3:17]

Participants

8

Reactant 4

HCID 78262Ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylateHCID 791372-Butenoic acid, 3-ethoxy-, ethyl esterHCID 521998p-Toluenesulfonic acid monohydrateHCID 2723922Sodium ethoxide

Product 1

HCID 178469202HCID 178469202, compoundYield 58.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 7237O-XyleneSolvent

Conditions

Temperature
165 °C

Procedure

To a solution of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (33.8 g; 150 mmol) and ethyl-3-ethoxybut-2-enoate (25 g; 157.5 mmol) in xylene (600 mL) was added a catalytic amount of p-toluenesulfonic acid mono hydrate. The resulting reaction mixture was heated to reflux (temp. of bath 165° C.) equipped with a Dean-Stark trap and condenser to collect ethanol. After 18 h, the solution was cooled to room temperature, transferred to a dropping funnel and then added dropwise to a stirred solution of sodium ethoxide (21% in ethanol, 59 mL; 157.5 mmol) in ethanol (350 mL). The resulting solution is heated to reflux for 18 h and, after cooling, the volatiles were removed under reduced pressure to yield a black oil. This material was suspended in water (150 mL) and washed with diethylether (2×150 mL). The aqueous phase was separated, cooled at 0° C. and slowly acidified to pH 4 with a 1N HCl with rapid stirring. The resulting precipitate was filtered, washed with diluted hydrochloric acid solution and dried to furnish 25.5 g (58%) of the title compound as a black solid.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. customequipped with a Dean-Stark trap and condenser
  4. customto collect ethanol
  5. temperaturethe solution was cooled to room temperature
  6. customtransferred to a dropping funnel
  7. temperatureThe resulting solution is heated
  8. temperatureto reflux for 18 h
  9. temperatureafter cooling
  10. customthe volatiles were removed under reduced pressure
  11. customto yield a black oil
  12. washwashed with diethylether (2×150 mL)
  13. customThe aqueous phase was separated
  14. temperaturecooled at 0° C.
  15. filtrationThe resulting precipitate was filtered
  16. washwashed with diluted hydrochloric acid solution
  17. customdried

Sources & evidence

ORD record
ord-009af61522aa48b086a1955f5306c04c
Source dataset
uspto-grants-2014_07
Patent number
US08785638B2

Reaction notes

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