Methanol → (1RS,2SR,6RS)-2-Hydroxymethyl-8-azabicyclo[4.3.0]non-4-ene

HRID 850715Notes

Reaction equation

HRID 850715 reaction equation
O=[C:2]1[CH:10]2[CH:5]([CH:6]=[CH:7][CH2:8][CH:9]2[C:11](OCC)=[O:12])[CH2:4][NH:3]1.[H-].C([Al+]CC(C)C)C(C)C.CO.COC(C)(C)C>O1CCCC1.O>[OH:12][CH2:11][CH:9]1[CH2:8][CH:7]=[CH:6][CH:5]2[CH:10]1[CH2:2][NH:3][CH2:4]2

Participants

7

Reactant 4

HCID 887MethanolHCID 15413tert-Butyl methyl etherHCID 21225700DiisobutylaluminumhydrideHCID 54398625ethyl (1RS,2RS,6RS)-9-oxo-8-azabicyclo[4.3.0]non-4-ene-2-carboxylate2×

Product 1

HCID 19364990(1RS,2SR,6RS)-2-Hydroxymethyl-8-azabicyclo[4.3.0]non-4-ene

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

5.2 g (25 mmol) of ethyl (1RS,2RS,6RS)-9-oxo-8-azabicyclo[4.3.0]non-4-ene-2-carboxylate (product A from Example K.2.) are dissolved in 50 ml of tetrahydrofuran under a nitrogen atmosphere and 130 ml of a 1.5 molar di(isobutyl)aluminium hydride solution (195 mmol) are subsequently added dropwise. The solution is heated under reflux for 16 h. After the reaction is complete, 60 ml of methanol, 30 ml of tert-butyl methyl ether and 10 ml of water are added dropwise successively and filtration with suction is then carried out in the presence of tonsil. The suction filter residue is stirred twice with a mixture of ethanol/conc. ammonia/water (10:1:1) and filtered off with suction once again. The combined filtrates are concentrated and the crude product is purified by chromatography (eluent: dichloromethanel-methanol/conc. ammonia 2:4:1).

Workup

  1. temperatureThe solution is heated
  2. temperatureunder reflux for 16 h
  3. filtrationfiltration with suction
  4. filtrationThe suction filter residue
  5. filtrationammonia/water (10:1:1) and filtered off with suction once again
  6. concentrationThe combined filtrates are concentrated
  7. customthe crude product is purified by chromatography (eluent: dichloromethanel-methanol/conc. ammonia 2:4:1)

Sources & evidence

ORD record
ord-1caa9648b4ed44fead0a579ceb6c8b2a
Source dataset
uspto-grants-2000_01
Patent number
US06018054

Reaction notes

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