Methyl iodide → 5-Ethyl-4-phenyl-thiophene-2-carboxylic acid

HRID 552276Notes

Reaction equation

HRID 552276 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:12]([OH:14])=[O:13])[S:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li][CH2:16][CH2:17]CC.IC>C1COCC1>[CH2:16]([C:11]1[S:10][C:9]([C:12]([OH:14])=[O:13])=[CH:8][C:7]=1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH3:17]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 12231844-Phenylthiophene-2-carboxylic acidHCID 178418339Butyllithium

Product 1

HCID 671664215-Ethyl-4-phenyl-thiophene-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

At −78° C., a solution of 4-phenylthiophene-2-carboxylic acid (800 mg, 3.92 mmol) in THF (10 mL) is treated with tert.-BuLi (8 mL, 1.6 M in pentane). The mixture is stirred at −70° C. for 40 min before iodomethane (1 mL) is added. Stirring is continued for 5 h at −78° C., then the reaction mixture is allowed to warm to rt overnight. The reaction is quenched with sat. aq. NH4Cl and extracted with EA. The organic extract is dried over MgSO4, the solvent is removed and the crude product is purified by CC on silica gel eluting with DCM containing 3% of methanol to give 5-ethyl-4-phenyl-thiophene-2-carboxylic acid (340 mg) as a red solid; LC-MS: tR=0.95 min, [M+1+MeCN]+=274.15; 1H NMR (CDCl3): δ 7.79 (s, 1H), 7.46-7.31 (m, 5), 2.92 (q, J=7.6 Hz, 2H), 1.30 (t, J=7.6 Hz, 3H).

Workup

  1. additionis added
  2. customThe reaction is quenched with sat. aq. NH4Cl
  3. extractionextracted with EA
  4. extractionThe organic extract
  5. dry with materialis dried over MgSO4
  6. customthe solvent is removed
  7. customthe crude product is purified by CC on silica gel eluting with DCM containing 3% of methanol

Sources & evidence

ORD record
ord-de21b785213f4e0dab0ab4e16f655673
Source dataset
uspto-grants-2011_05
Patent number
US07951794B2

Reaction notes

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