Sodium borohydride → HCID 19873390, compound

HRID 466368Notes

Reaction equation

HRID 466368 reaction equation
[N:1]1([CH2:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=[CH:13][CH:12]=2)=[O:10])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[BH4-].[Na+]>CCO>[N:1]1([CH2:8][CH:9]([C:11]2[CH:12]=[CH:13][C:14]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=[CH:15][CH:16]=2)[OH:10])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydride3×HCID 19873371HCID 19873371, compound

Product 1

HCID 19873390HCID 19873390, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a nitrogen covered mixture of 1.39 g (4.01 mmol) of the ketone, N-[4-[2-(Hexahydro-1H-azepin-1-yl)-1-oxoethyl]phenyl]methanesulfonamide from Preparation 7 in 25 ml of absolute EtOH, cooled in a cold bath is added 0.332 g (8.78 mmol) of sodium borohydride in portions over 10 min. Stirring is continued in the cold for 15 min and at ambient temperature for 2.5 hrs and an additional 0.193 g (5.10 mmol) of sodium borohydride is added. After stirring for an additional 1.5 hrs at ambient temperature, there is added an additional 0.202 g (5.34 mmol) of sodium borohydride. At the end of a total of 6 hrs, a suspended solid is collected on a filter, washed with EtOH and the combined filtrates are concentrated in vacuo. A solution of the residue in 25 ml of H2O is cooled in an ice bath, acidified to pH 3 with 2.5N HCl, washed twice with EtOAc, and then made basic with solid NaHCO3. The mixture is then saturated with NaCl and extracted four times with CH2Cl2. The combined extracts are washed with dilute brine, dried over MgSO4 and concentrated in vacuo. The residue is chromatographed on a 150 ml silica gel column (elution with 5% MeOH:CH2Cl2 containing 0.5% NH4OH) and 4.8 ml fractions are collected. Fractions at approximately 138-290 are combined and recrystallized from EtOAc to yield the title compound in two crops. M.p. 123°-124° C. and m.p. 120°-122.5° C.

Workup

  1. temperaturecooled in a cold bath
  2. customcold for 15 min
  3. stirringAfter stirring for an additional 1.5 hrs at ambient temperature
  4. customAt the end of a total of 6 hrs, a suspended solid is collected on a filter
  5. washwashed with EtOH
  6. concentrationthe combined filtrates are concentrated in vacuo
  7. temperatureA solution of the residue in 25 ml of H2O is cooled in an ice bath
  8. washwashed twice with EtOAc
  9. extractionsaturated with NaCl and extracted four times with CH2Cl2
  10. washThe combined extracts are washed with dilute brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customThe residue is chromatographed on a 150 ml silica gel column (elution with 5% MeOH:CH2Cl2 containing 0.5% NH4OH) and 4.8 ml fractions
  14. customare collected
  15. customrecrystallized from EtOAc

Sources & evidence

ORD record
ord-efece92a974b4659ad68e0ebd29dce01
Source dataset
uspto-grants-1992_10
Patent number
US05155268

Reaction notes

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