Ammonia → (2',3'-Dihydrospiro[[1,3]dioxolane-2,1'-inden]-5'-yl)methanol

HRID 2252262Notes

Reaction equation

HRID 2252262 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7]1([O:14][CH2:13][CH2:12][O:11]1)[CH2:6][CH2:5]2.C([Li])CCC.CN(C)[CH:22]=[O:23].[BH4-].[Na+].N>O1CCCC1.CO.O>[C:7]12([O:14][CH2:13][CH2:12][O:11]1)[C:8]1[C:4](=[CH:3][C:2]([CH2:22][OH:23])=[CH:10][CH:9]=1)[CH2:5][CH2:6]2

Participants

9

Reactant 5

HCID 222AmmoniaHCID 6228DimethylformamideHCID 4311764Sodium borohydrideHCID 451588945-Bromo-1,1-(ethylenedioxo)-indaneHCID 178418339Butyllithium

Product 1

HCID 69201996(2',3'-Dihydrospiro[[1,3]dioxolane-2,1'-inden]-5'-yl)methanol

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of Example 332A (13 g, 50.9 mmol) in tetrahydrofuran (150 mL) was added a 2.5 M solution of n-butyllithium in hexanes (30.5 mL, 76.4 mmol) dropwise at about −78° C. Then a solution of N,N-dimethylformamide (39.4 mL, 509.0 mmol) in tetrahydrofuran (40 mL) was added dropwise and the mixture was allowed to warm to ambient temperature. The mixture was poured into water and was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, filtered, and evaporated in vacuum. The residue was re-dissolved in a mixture of tetrahydrofuran (15 mL) and methanol (150 mL) and sodium borohydride (2.6 g, 68.7 mmol) was added in portions at about 0° C. The reaction mixture was stirred at room temperature for about 2 hours, then the mixture was concentrated in vacuum, diluted with water, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), filtered and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel using hexane/ethyl acetate (2:1) as the mobile phase to give the above intermediate. MS (DCI/NH3): m/z 207 (M+H)+.

Workup

  1. extractionwas extracted with ethyl acetate
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuum
  6. additionwas added in portions at about 0° C
  7. concentrationthe mixture was concentrated in vacuum
  8. additiondiluted with water
  9. extractionextracted with ethyl acetate
  10. washThe combined organic extracts were washed with brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customevaporated under reduced pressure
  14. customThe residue was purified by flash column chromatography on silica gel
  15. customto give the above intermediate

Sources & evidence

ORD record
ord-6cf72de5251541b9a924249bb7ecd109
Source dataset
uspto-grants-2008_01
Patent number
US07320986B2

Reaction notes

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