Hydrochloric Acid → HCID 178418753, compound

HRID 10711Notes

Reaction equation

HRID 10711 reaction equation
[C:1]([C:4]1[CH:13]=[C:12]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[C:11]([O:19][CH3:20])=[CH:10][C:5]=1[O:6][CH2:7][C:8]#[N:9])(=[O:3])C.C(O)(C)C.[N-:25]=[N+:26]=[N-:27].[Na+].Cl>O.C(OCC)(=O)C.[Br-].[Zn+2].[Br-].O1CCCC1>[CH3:20][O:19][C:11]1[C:12]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:13][C:4]([CH:1]=[O:3])=[C:5]([O:6][CH2:7][C:8]2[NH:9][N:27]=[N:26][N:25]=2)[CH:10]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 3776Isopropanol2×HCID 33557Sodium AzideHCID 21980975(2-Acetyl-5-methoxy-4-thiophen-2-yl-phenoxy)acetonitrile

Product 1

HCID 178418753HCID 178418753, compoundYield 65%

Reagents, catalysts & solvents 4

HCID 10421208Zinc bromideCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ex-89B: (2-Acetyl-5-methoxy-4-thiophen-2-yl-phenoxy)-acetonitrile (Ex-89A, 0.30 g, 1.1 mmol) was slurried in a mixture of water:isopropanol (3 mL, 2:1) to obtain a well-dispersed solution. Sodium azide (0.079 g, 1.2 mmol) followed by zinc bromide (0.25 g, 1.1 mmol) were added and the reaction was heated to reflux and vigorously stirred for 24 h. Additional solvent (1 mL, 1:1 water:isopropanol) was added after 10 h at reflux due to evaporation. The reaction was diluted with an ethyl acetate:tetrahydrofuran mixture (25 mL, 2:1) and a 3 N HCl solution (10 mL) and vigorously stirred until a homogenous solution was obtained (1 h). The layers were separated and the aqueous was extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried over sodium sulfate and concentrated to a dark green solid. Silica gel chromatography (15% methanol/methylene chloride containing 1% acetic acid) gave 0.22 g (65%) of 4-methoxy-2-(1H-tetrazol-5-ylmethoxy)-5-thiophen-2-yl-benzaldehyde as a pale green solid. 1H-NMR (300 MHz, DMSO-d6) δ 10.33 (s, 1H), 7.97 (s, 1H), 7.52–7.56 (m, 2H), 7.10–7.12 (m, 2H), 5.81 (s, 2H), 4.05 (s, 3H). MS (ESI) m/z=317 ([M+H]+, 100%), HRMS (ESI) Calcd. for C27H25NO7S: 317.0708. Found: 317.0712.

Workup

  1. additionwere added
  2. temperaturethe reaction was heated
  3. temperatureto reflux
  4. temperatureat reflux due to evaporation
  5. customwas obtained (1 h)
  6. customThe layers were separated
  7. extractionthe aqueous was extracted with ethyl acetate (3×50 mL)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. concentrationconcentrated to a dark green solid

Sources & evidence

ORD record
ord-fe789f3e21504dca864cbca9d901392b
Source dataset
uspto-grants-2006_08
Patent number
US07094801B2

Reaction notes

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