Water → methyl 7-(2-methyl-1H-tetrazol-5-yl)-2,3-dihydro-1-benzoxepine-4-carboxylate

HRID 2228303Notes

Reaction equation

HRID 2228303 reaction equation
[NH:1]1[C:5]([C:6]2[CH:7]=[CH:8][C:9]3[O:15][CH2:14][CH2:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]=3[CH:20]=2)=[N:4][N:3]=[N:2]1.[H-].[Na+].[CH3:23]I.O>CN(C=O)C>[CH3:23][N:3]1[NH:2][N:1]=[C:5]([C:6]2[CH:7]=[CH:8][C:9]3[O:15][CH2:14][CH2:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]=3[CH:20]=2)[NH:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178496911HCID 178496911, compound

Product 1

HCID 18472406methyl 7-(2-methyl-1H-tetrazol-5-yl)-2,3-dihydro-1-benzoxepine-4-carboxylateYield 79.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In DMF (6 ml) was dissolved methyl 7-(1H-tetrazol-5-yl)-2,3-dihydro-1-benzoxepine-4-carboxylate (400 mg, 1.47 mmol), and to the mixture was added at 0° C. sodium hydride (60%, 90 mg, 2.3 mmol). The mixture was stirred at the same temperature for 15 minutes, and to the mixture was added at 0° C. methyl iodide (0.28 ml, 4.4 mmol). While the temperature of the mixture was warmed from 0° C. to room temperature, the mixture was stirred for 3 hours. To the mixture was added at 0° C. water (30 ml), and the mixture was extracted with ethyl acetate. The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified with column chromatography (silica gel 40 g, ethyl acetate/hexane=1/8→1/2), and the first eluted desired fraction was concentrated under reduced pressure to give methyl 7-(2-methyl-1H-tetrazol-5-yl)-2,3-dihydro-1-benzoxepine-4-carboxylate (334 mg, 1.17 mmol, 79%). The second eluted desired fraction was concentrated under reduced pressure to give methyl 7-(1-methyl-1H-tetrazol-5-yl)-2,3-dihydro-1-benzoxepine-4-carboxylate (76 mg, 0.27 mmol, 18%). Methyl 7-(2-methyl-1H-tetrazol-5-yl)-2,3-dihydro-1-benzoxepine-4-carboxylate; IR (KBr): 1705 cm−1.

Workup

  1. temperatureWhile the temperature of the mixture was warmed from 0° C. to room temperature
  2. stirringthe mixture was stirred for 3 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified with column chromatography (silica gel 40 g, ethyl acetate/hexane=1/8→1/2)
  7. washthe first eluted desired fraction
  8. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-5973f514c2f940c280cd83e193f6b72f
Source dataset
uspto-grants-2002_07
Patent number
US06413947B1

Reaction notes

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