Dicyclohexylcarbodiimide → HCID 178513960, compound

HRID 2413706Notes

Reaction equation

HRID 2413706 reaction equation
Br.Br.[NH2:3][C@H:4]([C:11]([N:13]1[CH2:20][CH2:19][CH2:18][C@H:14]1[C:15]([NH2:17])=[O:16])=[O:12])[CH2:5][C:6]1[N:10]=[CH:9][NH:8][CH:7]=1.C([O:23][CH2:24][N:25]1[C:28](=[O:29])[CH2:27][C@H:26]1[C:30](O)=[O:31])=O.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.C(N(CC)CC)C>[OH2:12].[NH3:3].[OH:23][CH2:24][N:25]1[C:28](=[O:29])[CH2:27][C@H:26]1[C:30]([NH:3][C@H:4]([C:11]([N:13]1[CH2:20][CH2:19][CH2:18][C@H:14]1[C:15]([NH2:17])=[O:16])=[O:12])[CH2:5][C:6]1[N:10]=[CH:9][NH:8][CH:7]=1)=[O:31]

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 53923542HCID 53923542, compoundHCID 178419276HCID 178419276, compound

Product 2

HCID 12896473Azane;hydrateHCID 178513960HCID 178513960, compoundYield 116.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-10 °C

Procedure

In 26 ml of dry DMF was suspended 1.569 g of compound (4) and 1.187 ml of triethylamine was dropwise added slowly to the suspension at -15° to -10° C. After stirring the mixture at the same temperature for 30 minutes, insoluble matters were filtered off under cooling to obtain a clear filtrate. The filtrate was cooled to -10° C. and, a solution of 657.8 mg of compound (17) and 667 mg of HOBT in 20 ml of dry DMF was dropwise added gradually to the filtrate. Then, 861 mg of DCC was added thereto. After stirring the mixture for 2 hours at -10° to 0° C., the mixture was allowed to stand overnight in a refrigerator. The temperature was elevated to room temperature again and the precipitated crystals were filtered off. The solvent of the filtrate was removed by distillation under reduced pressure and the thus obtained residue was purified by column chromatography using 200 ml of silica gel (Wakogel C-200). By eluting with ethyl acetate-methanol-conc. ammonia water (60:30:3), 840 mg of Nα -[(S)-1-hydroxymethyl-4-oxo-2-azetidinylcarbonyl]-L-histidyl-L-prolinamide (18) was obtained.

Workup

  1. additionwas dropwise added slowly to the suspension at -15° to -10° C
  2. filtrationinsoluble matters were filtered off
  3. temperatureunder cooling
  4. customto obtain a clear filtrate
  5. stirringAfter stirring the mixture for 2 hours at -10° to 0° C.
  6. waitto stand overnight in a refrigerator
  7. customwas elevated to room temperature
  8. filtrationthe precipitated crystals were filtered off
  9. customThe solvent of the filtrate was removed by distillation under reduced pressure
  10. customthe thus obtained residue was purified by column chromatography
  11. washBy eluting with ethyl acetate-methanol-conc

Sources & evidence

ORD record
ord-2510e8f9184148429375b5546c5c9572
Source dataset
uspto-grants-1988_01
Patent number
US04719207

Reaction notes

Loading…