Sodium borohydride → HCID 20187536, compound

HRID 2308737Notes

Reaction equation

HRID 2308737 reaction equation
[BH4-].[Na+].[Cl:3][C:4]1[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:21])[CH:14]([F:20])[N:15]2[CH:19]=[N:18][CH:17]=[N:16]2)=[CH:9][CH:8]=1>CO.O>[Cl:3][C:4]1[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([OH:21])[CH:14]([F:20])[N:15]2[CH:19]=[N:18][CH:17]=[N:16]2)=[CH:9][CH:8]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 20187535HCID 20187535, compound

Product 1

HCID 20187536HCID 20187536, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

With stirring, 0.6 g of sodium borohydride is added at 5°-10° C. to a suspension of 12.1 g of 1-[4-(2,4-dichlorophenoxy)phenyl]-2-fluoro-2-(1H-1,2,4-triazol-1-yl)ethanone in 100 ml of methanol and 2 ml of water and the resultant mixture is stirred further first for 1 hour at 5°-10° C. and then for 2 hours at room temperature, whereupon a clear solution gradually forms. This solution is then poured into ice-water and extracted twice with dichloromethane. The organic phase is separated, washed twice with water, dried over sodium sulfate, filtered and concentrated. The residue is purified by chromatography through a column of silica gel eluted with diethyl ether, affording the following three fractions: The first fraction is concentrated by evaporation and the residue is recrystallised from petroleum ether, affording beige crystals with a melting point of 138°-139° C. Analytic and spectroscopic data show the presence of the pure diastereoisomer A. The second fraction is also concentrated by evaporation and the residue is recrystallised from diethyl ether, affording beige crystals with a melting point of 115°-116° C. Spectroscopic data shows that a mixture of both diastereoisomers A and B (approx. 1:1) is obtained. Similar working up of the third fraction affords the third pure diastereoisomer B with a melting point of 107°-108° C.

Workup

  1. extractionextracted twice with dichloromethane
  2. customThe organic phase is separated
  3. washwashed twice with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by chromatography through a column of silica gel
  8. washeluted with diethyl ether
  9. customaffording the following three fractions
  10. concentrationThe first fraction is concentrated by evaporation
  11. customthe residue is recrystallised from petroleum ether
  12. customaffording beige crystals with a melting point of 138°-139° C
  13. concentrationThe second fraction is also concentrated by evaporation
  14. customthe residue is recrystallised from diethyl ether
  15. customaffording beige crystals with a melting point of 115°-116° C
  16. additionSpectroscopic data shows that a mixture of both diastereoisomers A and B (approx. 1:1)
  17. customis obtained
  18. customaffords the third pure diastereoisomer B with a melting point of 107°-108° C.

Sources & evidence

ORD record
ord-c1d8442146b547f89f75cc384746ef83
Source dataset
uspto-grants-1987_09
Patent number
US04690942

Reaction notes

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