Sodium borohydride → HCID 58423839, compound

HRID 1408841Notes

Reaction equation

HRID 1408841 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:15](=[CH:16][CH:17]=1)[O:14][C:7]1([CH2:12][CH2:11][C:10](=[O:13])[CH2:9][CH2:8]1)[CH2:6][C:5]2=[O:18].[BH4-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:15](=[CH:16][CH:17]=1)[O:14][C:7]1([CH2:8][CH2:9][CH:10]([OH:13])[CH2:11][CH2:12]1)[CH2:6][C:5]2=[O:18]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 58423853HCID 58423853, compound

Product 1

HCID 58423839HCID 58423839, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 25 mL round bottom flask was placed 6-bromospiro[chroman-2,1′-cyclohexane]-4,4′-dione (240 mg, 0.779 mmol) and it was dissolved in THF (7.8 mL). To this solution was added NaBH4 (30 mg, 0.789 mmol) and the reaction was allowed to stir at room temperature for 5 minutes. At that time, TLC indicated total consumption of the diketone. The reaction was diluted with water (10 mL) and ethyl acetate (10 mL) and it was allowed to stir for 15 minutes. The phases were separated and the aqueous phase was back-extracted with ethyl acetate twice (5 mL/each). The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated under reduce pressure. The crude material was purified by flash chromatography (ISCO, 40 g SiO2 cartridge, ethyl acetate/hexanes as the eluents). A 3:1 mixture of separable isomers formed. The less-polar product (judge by TLC) was cleanly separated by flash chromatography (ISCO, 40 g SiO2 cartridge, ethyl acetate/hexanes as the eluents) and use for further development. The corresponding fractions for less-polar product were combined and concentrated under reduce pressure yielding one of the isomers of 6-bromo-4′-hydroxyspiro[chroman-2,1′-cyclohexan]-4-one (58 mg, 0.187 mmol, 24% yield).

Workup

  1. customIn a 25 mL round bottom flask was placed
  2. customconsumption of the diketone
  3. additionThe reaction was diluted with water (10 mL) and ethyl acetate (10 mL) and it
  4. stirringto stir for 15 minutes
  5. customThe phases were separated
  6. extractionthe aqueous phase was back-extracted with ethyl acetate twice (5 mL/each)
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by flash chromatography (ISCO, 40 g SiO2 cartridge, ethyl acetate/hexanes as the eluents)
  12. additionA 3:1 mixture of separable isomers
  13. customformed
  14. customThe less-polar product (judge by TLC) was cleanly separated by flash chromatography (ISCO, 40 g SiO2 cartridge, ethyl acetate/hexanes as the eluents) and
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-714f213ad2774d37806731bd54e34a42
Source dataset
uspto-grants-2014_12
Patent number
US08921359B2

Reaction notes

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