Acetic Acid → 2,3-dihydro-1H-3a-aza-cyclopenta[a]inden-6-ol

HRID 397316Notes

Reaction equation

HRID 397316 reaction equation
C([Li])CCC.Br[C:7]1[CH:15]=[CH:14][C:13]2[N:12]3[CH2:16][CH2:17][CH2:18][C:11]3=[CH:10][C:9]=2[CH:8]=1.C([O:22]B(OC(C)C)OC(C)C)(C)C.C(O)(=O)C.OO>CCCCCC.O1CCCC1.C(OCC)C.O>[CH2:18]1[C:11]2=[CH:10][C:9]3[CH:8]=[C:7]([OH:22])[CH:15]=[CH:14][C:13]=3[N:12]2[CH2:16][CH2:17]1

Participants

10

Reactant 5

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 21531Triisopropyl borateHCID 230001226-Bromo-2,3-dihydro-1h-3a-aza-cyclopenta[a]indeneHCID 178418339Butyllithium

Product 1

HCID 230001292,3-dihydro-1H-3a-aza-cyclopenta[a]inden-6-olYield 94%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-50 °C

Procedure

187.5 mL of a 1.6M solution of n-butyllithium (0.30 mol) in n-hexane was added over 20 min to a cooled (−78° C.) solution of 47.2 g 6-bromo-2,3-dihydro-1H-3a-aza-cyclopenta[a]indene (0.20 mol) in 800 mL tetrahydrofuran. The resulting beige suspension was warmed to −50° C. and stirred at this temperature for 45 min. The mixture was cooled to −78° C., and 92.0 mL (0.40 mol) triisoproyl-borate was added over 10 min. The mixture was stirred 30 min at −78° C. and allowed to warm to 0° C. over 30 min. The slightly turbid mixture was stirred at 0-10° C. for 15 min and 100 mL (0.875 mol) 50% acetic acid were added dropwise. To the resulting solution were added over 15 min 30 mL of a 35% hydrogen peroxide solution (0.31 mol) at a temperature of 0-5° C. The mixture was stirred at 0° C. for 30 min and at room temperature for 1 h. The reaction mixture was diluted with 2500 mL diethyl ether and 1000 mL water. The phases were separated and the organic phase was washed with 1000 mL water, twice with 1000 mL 5% sodium thiosulfate, again with 1000 mL water and finally with 1000 mL brine, dried over sodium sulfate and concentrated under aspirator vacuum. The solid residue was stirred with 500 mL n-hexane for 1 h. The product was collected by filtration and dried to constant weight under aspirator vacuum at room temperature to yield 32.56 g (94%) of the title compound as beige crystals melting at 116-118° C.

Workup

  1. temperatureThe mixture was cooled to −78° C.
  2. stirringThe mixture was stirred 30 min at −78° C.
  3. temperatureto warm to 0° C. over 30 min
  4. stirringThe slightly turbid mixture was stirred at 0-10° C. for 15 min
  5. stirringThe mixture was stirred at 0° C. for 30 min and at room temperature for 1 h
  6. customThe phases were separated
  7. washthe organic phase was washed with 1000 mL water, twice with 1000 mL 5% sodium thiosulfate, again with 1000 mL water and finally with 1000 mL brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under aspirator vacuum
  10. stirringThe solid residue was stirred with 500 mL n-hexane for 1 h
  11. filtrationThe product was collected by filtration
  12. customdried to constant weight under aspirator vacuum at room temperature

Sources & evidence

ORD record
ord-50d237bcfc544ceb970ab9b79bc448db
Source dataset
uspto-grants-2003_08
Patent number
US06610685B2

Reaction notes

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