Phenyl isocyanate → 7a-(3-benzyl-5-isoxazolyl)-hexahydro-1H-pyrrolizine

HRID 3307

Reaction equation

HRID 3307 reaction equation
[C:1]1([CH2:7][CH2:8][N+:9]([O-:11])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(N=C=O)C=CC=CC=1.[C:21]([C:23]12[CH2:30][CH2:29][CH2:28][N:27]1[CH2:26][CH2:25][CH2:24]2)#[CH:22]>C1C=CC=CC=1>[CH2:7]([C:8]1[CH:22]=[C:21]([C:23]23[CH2:30][CH2:29][CH2:28][N:27]2[CH2:26][CH2:25][CH2:24]3)[O:11][N:9]=1)[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 7672Phenyl isocyanateHCID 802081-Nitro-2-phenylethaneHCID 195976957a-ethynylhexahydro-1H-pyrrolizine

Product 1

HCID 189347217a-(3-benzyl-5-isoxazolyl)-hexahydro-1H-pyrrolizineYield 52.2%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

2-Phenylnitroethane (895 mg, 5.92 mmol, from step 15b) and phenylisocyanate (1.3 mL, 11.8 mmol) were dissolved in benzene (12 mL) and added to a flask containing 7a-ethynyl-hexahydro-1H-pyrrolizine (400 mg, 2.96 mmol, from step 13a). The solution was stirred at reflux for 5 hours, cooled and stirred for 48 hours at room temperature. The mixture was filtered and extracted with 6N HCl. The aqueous phase was made basic with 15% NaOH and extracted with methylene chloride. The organic extracts were combined, dried (MgSO4) and concentrated. The residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford an amber oil (415 mg, 52%). 1H NMR (CDCl3, 300 MHz) δ1.71-1.92 (m, 6H), 2.11-2.23 (m, 2H), 2.58-2.66 (m, 2H), 3.08-3.15 (m, 2H), 3.95 (s, 2H), 5.87 (s, 1H), 7.20-7.34 (m, 5H); MS (CI/NH3) m/z: 269 (M+H)+.

Workup

  1. additionadded to a flask
  2. temperatureat reflux for 5 hours
  3. temperaturecooled
  4. stirringstirred for 48 hours at room temperature
  5. filtrationThe mixture was filtered
  6. extractionextracted with 6N HCl
  7. extractionextracted with methylene chloride
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1)

Sources & evidence

ORD record
ord-58fe89ee31bc421fa1afea328a51d6a8
Source dataset
uspto-grants-1998_03
Patent number
US05733912

Linked notes

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