HCID 15079650, compound → HCID 15079652, compound

HRID 476510Notes

Reaction equation

HRID 476510 reaction equation
N([O-])=[O:2].[Na+].N[C:6]1[CH:30]=[CH:29][C:9]([O:10][C:11]2[C:12]([Cl:28])=[CH:13][C:14]([F:27])=[C:15]([N:17]3[C:21](=[O:22])[N:20]([CH2:23][CH2:24][CH2:25][F:26])[N:19]=[N:18]3)[CH:16]=2)=[CH:8][CH:7]=1>O.S(=O)(=O)(O)O.C1(C)C(C)=CC=CC=1.C1(C)C=CC=CC=1.[O-]S([O-])(=O)=O.[Cu+2]>[Cl:28][C:12]1[C:11]([O:10][C:9]2[CH:8]=[CH:7][C:6]([OH:2])=[CH:30][CH:29]=2)=[CH:16][C:15]([N:17]2[C:21](=[O:22])[N:20]([CH2:23][CH2:24][CH2:25][F:26])[N:19]=[N:18]2)=[C:14]([F:27])[CH:13]=1

Participants

7

Reactant 2

HCID 15079650HCID 15079650, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 15079652HCID 15079652, compoundYield 28.2%

Reagents, catalysts & solvents 4

HCID 24462Copper SulfateCatalystHCID 962WaterSolvent2×HCID 1118Sulfuric AcidSolventHCID 21552640HCID 21552640, compoundSolvent

Procedure

While maintaining a temperature of 5° C. to 10° C., 1.03 g (0.015 mole) of sodiuM nitrite dissolved in 10 ml of water was added to a stirred mixture of 4.76 g (0.0125 mole) of 1-[5-(4-aminophenoxy)-4-chloro-2-fluorophenyl]-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-one (prepared by the method of Steps A and B of Example 1 in 6 ml of concentrated sulfuric acid. The resultant mixture was stirred at 6° C. for 30 minutes. This mixture was added to a refluxing mixture of 37.5 g (0.150-mole) of copper II sulfate in 70 ml of xylene/toluene (50/50) and 100 ml of water. After complete addition, the mixture was stirred and heated at reflux for one hour. The mixture was cooled to room temperature and the phases were allowed to separate. The organic phase was extracted with an aqueous sodium hydroxide solution (6.0 g of sodium hydroxide in 250 ml of water). The basic extract was acidified with concentrated hydrochloric acid forming a precipitate. This mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to yield 1.35 g of 1-[4-chloro-2-fluoro-5-(4-hydroxyphenoxy)phenyl]-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-one as a solid, m.p. 157°-159° C., compound 3 of Table 1.

Workup

  1. additionAfter complete addition
  2. temperatureheated
  3. temperatureat reflux for one hour
  4. customto separate
  5. extractionThe organic phase was extracted with an aqueous sodium hydroxide solution (6.0 g of sodium hydroxide in 250 ml of water)
  6. extractionThe basic extract
  7. extractionThis mixture was extracted with ethyl acetate
  8. dry with materialThe extract was dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-61fb1e8c04404d3db2cef5a721edebb5
Source dataset
uspto-grants-1989_12
Patent number
US04885025

Reaction notes

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