monoMethyl succinate → N-(3-carbonyl-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-succinamic acid methyl ester

HRID 1056839

Reaction equation

HRID 1056839 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=O.[NH2:10][C:11]1[S:12][C:13]2[CH2:22][CH2:21][CH2:20][CH2:19][C:14]=2[C:15]=1[C:16](N)=[O:17]>S(Cl)(Cl)=O.O1CCOCC1.O>[CH3:9][O:8][C:1](=[O:7])[CH2:2][CH2:3][C:4]([NH:10][CH:11]1[S:12][C:13]2[CH2:22][CH2:21][CH2:20][CH2:19][C:14]=2[C:15]1=[C:16]=[O:17])=[O:6]

Participants

6

Reactant 2

HCID 77487monoMethyl succinateHCID 2902232-Amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide

Product 1

HCID 118129686N-(3-carbonyl-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-succinamic acid methyl esterYield 48.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 24386Thionyl ChlorideSolventHCID 312751,4-DioxaneSolvent

Procedure

Monomethyl hydrogen succinate (4.7 g, 0.035 mol) was refluxed in thionyl chloride (20 ml) for 2 hrs. After consumption of starting material, excess of thionyl chloride was distilled off. The reaction mixture dissolved in dioxane (10 ml) and was added drop wise to 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide 1 (7 g, 0.035 moles) in dioxane (10 ml) at 0° C. and stirred at room temperature (R.T) for 2 hrs. The reaction mixture was diluted with water to give crude product which was filtered and washed with water. The crude was purified by chromatography on silica gel using 1:1 Ethyl acetate:Hexane to give 5 g (46%) of N-(3-carbonyl-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-succinamic acid methyl ester. 1H NMR (400 MHz, DMSO) δ ppm=1.72 (m, 4H), 2.6 (m, 4H), 2.68 (m, 4H), 3.59 (s, 3H), 6.99 (s, 1H), 7.55 (s, 1H), 11.48 (s, 1H). LC-MS: [M−H]=308.9.

Workup

  1. customAfter consumption of starting material
  2. distillationexcess of thionyl chloride was distilled off
  3. dissolutionThe reaction mixture dissolved in dioxane (10 ml)
  4. customto give crude product which
  5. filtrationwas filtered
  6. washwashed with water
  7. customThe crude was purified by chromatography on silica gel using 1:1 Ethyl acetate

Sources & evidence

ORD record
ord-97e473ca689a4404bc45d53705fd6edd
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Linked notes

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