Hydrochloric Acid → 1-[4-Methoxy-5-(5,6,7,8-tetrahydronaphthalen-2-yl)thiophen-3-yl]ethanone

HRID 337370Notes

Reaction equation

HRID 337370 reaction equation
CO[C:3]1[C:4](C#N)=[CH:5][S:6][C:7]=1[C:8]1[CH:17]=[CH:16][C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[CH:9]=1.[OH2:20].[CH3:21][Mg]Br.Cl.C([O:27][CH2:28][CH3:29])C>C(OCC)(=O)C>[CH3:21][O:20][C:3]1[C:4]([C:28](=[O:27])[CH3:29])=[CH:5][S:6][C:7]=1[C:8]1[CH:17]=[CH:16][C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[CH:9]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 3283Diethyl EtherHCID 681614114-Methoxy-5-(5,6,7,8-tetrahydronaphthalen-2-yl)thiophene-3-carbonitrileHCID 178418573HCID 178418573, compound

Product 1

HCID 681622951-[4-Methoxy-5-(5,6,7,8-tetrahydronaphthalen-2-yl)thiophen-3-yl]ethanoneYield 65%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To 3.51 g of 4-methoxy-5-(5,6,7,8-tetrahydronaphthalen-2-yl)thiophene-3-carbonitrile in diethyl ether (45 ml) cooled with water, 43.3 ml of methylmagnesium bromide (3.0 M diethyl ether solution) was added dropwise at room temperature over 5 minutes (exothemically). The reaction mixture was allowed to react at room temperature for 3 days and poured into 30 ml of concentrated hydrochloric acid diluted with 300 ml of ice-cold water and stirred at room temperature for 1 hour then on a water bath at 35° C. for 1 hour. After addition of 200 ml of ethyl acetate, the reaction mixture was allowed to separate, and the organic layer was collected. The aqueous layer was extracted with 100 ml of ethyl acetate three times, and the extracts were combined with the organic layer. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue (dark brown oil) was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/20→1/15) to obtain 2.44 g of the desired product (yield 65%).

Workup

  1. additionwas added dropwise at room temperature over 5 minutes (exothemically)
  2. customto react at room temperature for 3 days
  3. waiton a water bath at 35° C. for 1 hour
  4. customto separate
  5. customthe organic layer was collected
  6. extractionThe aqueous layer was extracted with 100 ml of ethyl acetate three times
  7. washThe organic layer was washed with saturated aqueous sodium chloride
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue (dark brown oil) was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/20→1/15)

Sources & evidence

ORD record
ord-e0fe76d7bbfa4181b742138801fd89ab
Source dataset
uspto-grants-2014_11
Patent number
US08889732B2

Reaction notes

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