Hydrochloric Acid → HCID 14720528, compound

HRID 1087358Notes

Reaction equation

HRID 1087358 reaction equation
[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH:2]=[CH2:3].N(OC(C)(C)C)=O.N[C:16]1[C:17]([Cl:33])=[CH:18][C:19]([F:32])=[C:20]([N:22]2[C:26](=[O:27])[N:25]([CH2:28][CH2:29][CH2:30][F:31])[N:24]=[N:23]2)[CH:21]=1.[ClH:34]>C(#N)C.[Cu](Cl)Cl>[Cl:34][CH:2]([CH2:3][C:16]1[CH:21]=[C:20]([N:22]2[C:26](=[O:27])[N:25]([CH2:28][CH2:29][CH2:30][F:31])[N:24]=[N:23]2)[C:19]([F:32])=[CH:18][C:17]=1[Cl:33])[C:1]([O:5][CH2:6][CH3:7])=[O:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8821Ethyl AcrylateHCID 10906Tert-Butyl nitriteHCID 145516171-(5-amino-4-chloro-2-fluorophenyl)-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-one

Product 1

HCID 14720528HCID 14720528, compound

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 6342AcetonitrileSolvent2×

Procedure

To an ice cold, stirred mixture of 5.54 g (0.0553 mole) of ethyl acrylate, 10 mL of acetonitrile, 0.43 g (0.0042 mole) of tert-butyl nitrite, and 0.45 g (0.0033 mole) of copper (II) chloride was added a solution of 0.80 g (0.0028 mole) of 1-(5-amino-4-chloro-2-fluorophenyl)-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-one (which may be prepared as described in International patent publication WO 87/03873, Example 1 A-E) in 10 mL of acetonitrile. The reaction mixture was stirred at room temperature for five hours and then was diluted with 2N hydrochloric acid. The acidic mixture was extracted with three portions of diethyl ether. The extracts were combined and dried over anhydrous magnesium sulfate. The dried organic phase was filtered and the filtrate was evaporated leaving a residue. This residue was purified by column chromatography on silica gel, eluting with n-heptane: ethyl acetate (2:1) to yield 1.1 g of ethyl 2-chloro-3-[2-chloro-4-fluoro-5-[4-(3-fluoropropyl)-1,4-dihydro-5-oxo-5H-tetrazol-1-yl]phenyl]propionate as an oil, compound 3 of Table 1.

Workup

  1. extractionThe acidic mixture was extracted with three portions of diethyl ether
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationThe dried organic phase was filtered
  4. customthe filtrate was evaporated
  5. customleaving a residue
  6. customThis residue was purified by column chromatography on silica gel
  7. washeluting with n-heptane: ethyl acetate (2:1)

Sources & evidence

ORD record
ord-69964a4e4e594954a133ad9a4d668472
Source dataset
uspto-grants-1991_07
Patent number
US05035740

Reaction notes

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