1,8-Diazabicyclo(5.4.0)undec-7-ene → 2-Benzyloxycarbonylamino-3-bicyclo[2.2.1]hept-7-yl-acrylic acid methyl ester

HRID 19362Notes

Reaction equation

HRID 19362 reaction equation
[CH3:1][O:2][C:3](=[O:20])[CH:4](P(O)(O)=O)[NH:5][C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7].N12CCCN=C1CCCCC2.[CH:32]12[CH:38]([CH:39]=O)[CH:35]([CH2:36][CH2:37]1)[CH2:34][CH2:33]2>ClCCl>[CH3:1][O:2][C:3](=[O:20])[C:4]([NH:5][C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])=[CH:39][CH:38]1[CH:35]2[CH2:36][CH2:37][CH:32]1[CH2:33][CH2:34]2

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 66895383N-(benzyloxycarbonyl)-alpha-phosphonoglycine methyl esterHCID 84647822Bicyclo[2.2.1]heptane-7-carbaldehyde

Product 1

HCID 668952242-Benzyloxycarbonylamino-3-bicyclo[2.2.1]hept-7-yl-acrylic acid methyl esterYield 33.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

In a round bottom flask was placed N-(benzyloxycarbonyl)-α-phosphonoglycine methyl ester (680 mg, 2.05 mmol) in dichloromethane (5 mL) and cooled to 0° C. in an ice bath. To this mixture was added slowly 1,8-diazabicyclo[5.4.0]undec-7-ene (266 μL, 1.78 mmol) and stirred at 0° C. for 20 min. The mixture was treated with a solution of bicyclo[2.2.1]heptane-7-carbaldehyde (170 mg, 1.36 mmol) in dichloromethane (5 mL). After the addition was complete, the mixture was allowed to warm to 25° C. and stirred overnight. The mixture was concentrated in vacuo and the residue taken up in ethyl acetate (50 mL) and washed with a saturated aqueous ammonium chloride solution (2×25 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. Purification by AnaLogix IntelliFlash flash chromatography (4 g column, 5% ethyl acetate/hexanes to 20% ethyl acetate/hexanes) afforded 2-benzyloxycarbonylamino-3-bicyclo[2.2.1]hept-7-yl-acrylic acid methyl ester (150 mg, 33%) as a clear colorless oil.

Workup

  1. customIn a round bottom flask was placed
  2. additionAfter the addition
  3. temperatureto warm to 25° C.
  4. stirringstirred overnight
  5. concentrationThe mixture was concentrated in vacuo
  6. washwashed with a saturated aqueous ammonium chloride solution (2×25 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customPurification by AnaLogix IntelliFlash flash chromatography (4 g column, 5% ethyl acetate/hexanes to 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-2003b65193e64a248d4a13433853fe1e
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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