Dicyclohexylcarbodiimide → HCID 53837275, compound

HRID 484948Notes

Reaction equation

HRID 484948 reaction equation
[CH3:1]N(C1C=CC=CN=1)C.[C:10]([NH:20][C@H:21]([C:24]([OH:26])=O)[CH2:22][OH:23])([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11].[NH:27]1[CH2:30][CH:29]([C:31]([OH:33])=[O:32])[CH2:28]1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(N(CC)CC)C.CO.C(O)(=O)C>[CH3:1][O:32][C:31]([CH:29]1[CH2:30][N:27]([C:24](=[O:26])[C@H:21]([CH2:22][OH:23])[NH:20][C:10]([O:12][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[O:11])[CH2:28]1)=[O:33]

Participants

9

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 218852-DimethylaminopyridineHCID 931923-azetidinecarboxylic AcidHCID 100310N-(Benzyloxycarbonyl)-L-serine

Product 1

HCID 53837275HCID 53837275, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
28 °C

Procedure

3.37 g of triethylamine and 0.37 g of dimethylaminopyridine were added to a stirred mixture of 7.18 g of N-carbobenzyloxy-L-serine and 5.00 g of 1B in 150 ml of dry tetrahydrofuran at 0° C. under nitrogen. The stirred mixture was allowed to warm to about 5° C. (10 minutes), 6.19 g of N,N'-dicyclohexylcarbodiimide was added, heat being evolved, and the mixture was allowed to warm to 28° C. and held there (25 minutes). The mixture was stirred at room temperature over a weekend, when 3 ml of glacial acetic acid and 15 ml of methanol were added and the mixture was stirred at room temperature for 2.5 hours. Then sufficient triethylamine was added to make the mixture pH=7, the mixture was filtered and the solvents were evaporated from the filtrate under reduced pressure. The residue was mixed with 50 ml of methanol and 100 ml of ethyl acetate and filtered, and the solvents were evaporated from the filtrate under reduced pressure. The residue was flash-chromatographed, first with ethyl acetate as eluent to remove high Rf minor impurities, then a 9:1 v:v mixture of ethyl acetate and methanol. The solvents were evaporated, the residue was recrystallized from methylene chloride and hexane, and the product was held under very low pressure (<1 Torr.) overnight to give the N-(N-carbobenzyloxy-L-seryl)-3-azetidinecarboxylic acid methyl ester (1C), as a very hygroscopic, colorless solid, m.p.: 90°-95° C.

Workup

  1. additionwas added
  2. temperatureheat
  3. custom(25 minutes)
  4. stirringthe mixture was stirred at room temperature for 2.5 hours
  5. filtrationthe mixture was filtered
  6. customthe solvents were evaporated from the filtrate under reduced pressure
  7. additionThe residue was mixed with 50 ml of methanol and 100 ml of ethyl acetate
  8. filtrationfiltered
  9. customthe solvents were evaporated from the filtrate under reduced pressure
  10. customThe residue was flash-chromatographed, first with ethyl acetate as eluent
  11. customto remove high Rf minor impurities
  12. additiona 9:1 v:v mixture of ethyl acetate and methanol
  13. customThe solvents were evaporated
  14. customthe residue was recrystallized from methylene chloride and hexane
  15. customwas held under very low pressure (<1 Torr.) overnight

Sources & evidence

ORD record
ord-5d5b794032cc40ef8245428ad919697a
Source dataset
uspto-grants-1985_08
Patent number
US04534787

Reaction notes

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