Dicyclohexylcarbodiimide → HCID 178516326, compound

HRID 980370Notes

Reaction equation

HRID 980370 reaction equation
[CH:1]1C=C[C:4]2N(O)N=[N:7][C:5]=2[CH:6]=1.C1CCC(N=C=NC2CCCCC2)CC1.[CH2:26]([O:33][C:34](=[O:50])[C@@H:35]1[CH2:39][CH2:38][CH2:37][N:36]1[C:40](=[O:49])[C@H:41]([CH2:43][C:44]1[N:48]=[CH:47][NH:46][CH:45]=1)[NH2:42])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[OH2:51].C[OH:53]>ClCCl>[CH2:26]([O:33][C:34](=[O:50])[C@@H:35]1[CH2:39][CH2:38][CH2:37][N:36]1[C:40](=[O:49])[C@H:41]([CH2:43][C:44]1[N:48]=[CH:47][NH:46][CH:45]=1)[NH:42][C:4]([C@H:5]1[NH:7][C:1](=[O:53])[CH2:6]1)=[O:51])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 22242641Methanol--water (1/1)HCID 178511788HCID 178511788, compound

Product 1

HCID 178516326HCID 178516326, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In 30 ml of dichloromethane was suspended 455 mg of compound (2) and after adding thereto 801 mg of HOBT and 1.059 g of DCC and stirring the mixture for 15 minutes, the reaction was maintained for 15 minutes at room temperature. The reaction mixture was ice-cooled again and then 50 ml of a dichloromethane solution of foregoing compound (11) was added to the reaction mixture. After reacting the mixture for one hour under ice-cooling, the reaction was maintained overnight at room temperature. Precipitates thus formed was filtered off and the filtrate was concentrated to dryness. The residue thus obtained was dissolved in 20 ml of water-methanol (4:1) and subjected to HP-20 column chromatography. When the eluate by water-methanol (1:4) was concentrated to dryness, 1.135 g of crude Nα -[(S)-2-azetidinone-4-carbonyl]-L-histidyl-L-proline benzyl ester (12) was obtained. When the product was subjected to silica gel column chromatography again and eluted with chloroform-methanol-aqueous ammonia (40:10:1), 927 mg of the pure product (12) was obtained.

Workup

  1. additionafter adding
  2. temperaturecooled again
  3. customfor one hour
  4. temperaturecooling
  5. temperaturethe reaction was maintained overnight at room temperature
  6. customPrecipitates thus
  7. customformed
  8. filtrationwas filtered off
  9. concentrationthe filtrate was concentrated to dryness
  10. customThe residue thus obtained
  11. concentrationWhen the eluate by water-methanol (1:4) was concentrated to dryness

Sources & evidence

ORD record
ord-3b2325f2813648ec9f3d202b4caedf64
Source dataset
uspto-grants-1987_01
Patent number
US04636567

Reaction notes

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