Hydrochloric Acid → HCID 178470750, compound

HRID 2276341Notes

Reaction equation

HRID 2276341 reaction equation
[O-]CC.[Na+].[NH2:5][C:6]1[S:10][C:9]2[CH2:11][CH2:12][CH2:13][CH2:14][C:8]=2[C:7]=1[C:15]([C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)=O.[C:24](OCC)(=[O:32])[CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].Cl>C(O)C.O>[CH2:30]([O:29][C:27](=[O:28])[CH2:26][C:25]1[C:15]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)=[C:7]2[C:8]3[CH2:14][CH2:13][CH2:12][CH2:11][C:9]=3[S:10][C:6]2=[N:5][C:24]=1[OH:32])[CH3:31]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 31249Diethyl SuccinateHCID 754850(2-Amino-4,5,6,7-tetrahydro-1-benzothien-3-yl)(4-methylphenyl)methanoneHCID 2723922Sodium ethoxide

Product 1

HCID 178470750HCID 178470750, compoundYield 23.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of sodium ethoxide 21% in ethanol (1.8 mL; 4.8 mmol) in dry ethanol (30 mL) under a nitrogen atmosphere was added (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(p-tolyl)methanone (1.09 g; 4 mmol) and diethyl succinate (0.929 mL; 5.6 mmol). The mixture was heated to 100° C. for 24 h. The reaction mixture was dissolved with water (8 ml) and acidified with a solution of hydrochloric acid 1N to pH 1 and the aqueous layer was extracted with ethyl acetate. The organics were combined, dried over sodium sulphate and concentrated under reduced pressure. The crude was suspended in dry ethanol (30 mL) and a catalytic amount of concentrated sulfuric acid (10 drops) was carefully added. The reaction mixture was heated to reflux for 21 h. The volatiles were removed under reduced pressure and the remaining residue was purified by flash-chromatography on silica gel using a gradient of methanol (1-20%) in ethyl acetate as eluent to furnish 0.358 g (19.6%) of ethyl[2-hydroxy-4-(p-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate as an ochre solid. ESI/APCI(+): 382 (M+H).

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate
  2. dry with materialdried over sodium sulphate
  3. concentrationconcentrated under reduced pressure
  4. additiona catalytic amount of concentrated sulfuric acid (10 drops) was carefully added
  5. temperatureThe reaction mixture was heated
  6. temperatureto reflux for 21 h
  7. customThe volatiles were removed under reduced pressure
  8. customthe remaining residue was purified by flash-chromatography on silica gel using a gradient of methanol (1-20%) in ethyl acetate as eluent

Sources & evidence

ORD record
ord-96a11ca33be04fd4ae7d4ae722a7f6d9
Source dataset
uspto-grants-2015_09
Patent number
US09132129B2

Reaction notes

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