Dimethylformamide → 4-(2-Formyl-4-(4-methoxyphenyl)thiophen-3-yl)-3-methylbenzonitrile

HRID 536605Notes

Reaction equation

HRID 536605 reaction equation
[Li+].CC([N-]C(C)C)C.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:18]([C:22]3[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][C:23]=3[CH3:30])=[CH:19][S:20][CH:21]=2)=[CH:13][CH:12]=1.CN(C)[CH:33]=[O:34]>O1CCCC1>[CH:33]([C:19]1[S:20][CH:21]=[C:17]([C:14]2[CH:13]=[CH:12][C:11]([O:10][CH3:9])=[CH:16][CH:15]=2)[C:18]=1[C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][C:23]=1[CH3:30])=[O:34]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 2724682Lithium diisopropylamideHCID 672536684-(4-(4-Methoxyphenyl)thiophen-3-yl)-3-methylbenzonitrile

Product 1

HCID 866714924-(2-Formyl-4-(4-methoxyphenyl)thiophen-3-yl)-3-methylbenzonitrileYield 29.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of freshly prepared LDA (0.8 mL, 1.64 mmol) in anhydrous tetrahydrofuran (7 mL) was added slowly a solution of 4-(4-(4-methoxyphenyl)thiophen-3-yl)-3-methylbenzonitrile (Scheme I, 3, X1=4-methoxyphenyl, X2=4-cyano-2-methylphenyl) (500 mg, 1.637 mmol) in anhydrous tetrahydrofuran (6 mL) under nitrogen at −78° C. After being stirred for 15 min., a solution of dimethylformamide (0.14 mL, 1.804 mmol) in anhydrous tetrahydrofuran (3 mL) was dropwise added. The resulting mixture was stirred for 1 h at −78° C., and at room temperature for 3 h. The reaction was quenched with water (50 mL), and extracted with ethyl acetate (40 mL×3). The combined organic extracts were washed with water (30 mL), brine (50 mL), dried over anhydrous sodium sulfate, evaporated, and purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20:1) to afford 4-(2-formyl-4-(4-methoxyphenyl)thiophen-3-yl)-3-methylbenzonitrile (Scheme I, 4A, X1=4-methoxyphenyl, X2=4-cyano-2-methylphenyl) (0.16 g, yield 29.3%) as a white solid (confirmed by NOE). 1H NMR (DMSO-d6 400 MHz): δ 9.46 (s, 1H), 8.31 (d, J=1.2 Hz, 1H), 7.83 (s, 2H), 7.67 (d, J=8.8 Hz, 1H), 7.07 (d, J=8.8 Hz, 2H), 6.89 (d, J=8.8 Hz, 2H), 3.77 (s, 3H), 1.94 (s, 3H).

Workup

  1. stirringThe resulting mixture was stirred for 1 h at −78° C.
  2. waitat room temperature for 3 h
  3. customThe reaction was quenched with water (50 mL)
  4. extractionextracted with ethyl acetate (40 mL×3)
  5. washThe combined organic extracts were washed with water (30 mL), brine (50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. custompurified by column chromatography (silica gel, petroleum ether/ethyl acetate=20:1)

Sources & evidence

ORD record
ord-e5f36c20775049798febdd3153b83e71
Source dataset
uspto-grants-2014_10
Patent number
US08859611B2

Reaction notes

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