4-Hydroxybenzaldehyde → 5-(4-Formylphenoxy)thiophene-2-carbonitrile

HRID 747550Notes

Reaction equation

HRID 747550 reaction equation
F[C:2]1[S:6][C:5]([C:7]#[N:8])=[CH:4][CH:3]=1.[OH:9][C:10]1[CH:17]=[CH:16][C:13]([CH:14]=[O:15])=[CH:12][CH:11]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH:14]([C:13]1[CH:16]=[CH:17][C:10]([O:9][C:2]2[S:6][C:5]([C:7]#[N:8])=[CH:4][CH:3]=2)=[CH:11][CH:12]=1)=[O:15]

Participants

5

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 11430Potassium CarbonateHCID 108987265-fluorothiophene-2-carbonitrile

Product 1

HCID 586773735-(4-Formylphenoxy)thiophene-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Dissolve 5-fluorothiophene-2-carbonitrile (0.541 g, 4.25 mmol) and 4-hydroxybenzaldehyde (0.519 g, 4.25 mmol) in DMF (11 mL). Add K2CO3 (1.469 g, 10.6 mmol) and heat at 100° C. for 1.5 hours. Concentrate the reaction mixture. Take the solid up in ethyl acetate (100 mL) and wash with water (2×25 mL). Dry the organic layer over MgSO4, filter and concentrate. Purify by chromatography eluting with 30% ethyl acetate in hexanes to give the title compound: 1H NMR (CDCl3): 9.96 (s, 1H), 7.98 (dd, J=6.6, 2.2 Hz, 2H), 7.86 (d, J=4.0 Hz, 1H), 7.40 (d, J=2.2 Hz, 2H), 6.96 (d, J=4.0 Hz, 1H); HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=17.4 min, 98.1% purity.

Workup

  1. concentrationConcentrate the reaction mixture
  2. washwash with water (2×25 mL)
  3. dry with materialDry the organic layer over MgSO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify by chromatography
  7. washeluting with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-9b58e47c87894322880907dc01238d42
Source dataset
uspto-grants-2008_07
Patent number
US07396943B2

Reaction notes

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