Dicyclohexylcarbodiimide → HCID 44385635, compound

HRID 1982634Notes

Reaction equation

HRID 1982634 reaction equation
C1(COC(=O)[NH:10][C@H:11]([CH2:16][O:17][CH2:18][C:19]([NH2:21])=[O:20])[CH2:12][CH:13]([CH3:15])[CH3:14])C=CC=CC=1.[H][H].[C:25]([N:35]1[CH2:42][CH2:41][CH2:40][C@H:36]1[C:37]([OH:39])=O)([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>[Pd].CO>[NH2:21][C:19](=[O:20])[CH2:18][O:17][CH2:16][CH:11]([NH:10][C:37]([CH:36]1[CH2:40][CH2:41][CH2:42][N:35]1[C:25]([O:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26])=[O:39])[CH2:12][CH:13]([CH3:14])[CH3:15]

Participants

8

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 101987Benzyloxycarbonyl-L-prolineHCID 53972355HCID 53972355, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 44385635HCID 44385635, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A stirred suspension of 1.58 g (0.0051 mol) of (S)-phenylmethyl-[1-[(2 amino-2-oxoethoxy)methyl]-3-methylbutyl]carbamate and 0.3 g of 20% palladium on carbon in a 100 ml of methanol is exposed to hydrogen gas for 15 minutes, the suspension is purged with nitrogen gas, filtered, and the solvent evaporated in vacuo at 30° C. The residue is dissolved in 100 ml of dichloromethane, the solution is cooled to 0° C. and 1.3 g (0.0051 mol) of carbobenzyloxyproline, 0.78 g (0.0051 mol) of 1-hyroxybenzotriazole and 1.1 g (0.0051 mol) of dicyclohexylcarbodiimide are added. The mixture is allowed to reach room temperature and stirred for 14 hours, filtered, the solvent evaporated in vacuo and the residue dissolved in 200 ml of dichloromethane and washed successively with a 5% aqueous solution of sodium carbonate, 2×200 ml, 10% aqueous solution of citric acid, 2×200 ml and a saturated aqueous solution of sodium chloride, 2×200 ml. The dichloromethane layer is separated, dried over sodium sulfate, evaporated in vacuo and the residue purified by chromatography using silica gel and eluting with dichloromethane-methanol (95:5) to give [S-(R*,R*)]-phenylmethyl 2[[[1-[(2-amino-2-oxoethoxy)methyl]-3-methylbutyl]amino]carbonyl]-1-pyrrolidinecarboxylate, 1.1 g; mp 146°-148°; [α]D25 -55.3° (c 1.31, methanol).

Workup

  1. customthe suspension is purged with nitrogen gas
  2. filtrationfiltered
  3. customthe solvent evaporated in vacuo at 30° C
  4. dissolutionThe residue is dissolved in 100 ml of dichloromethane
  5. customto reach room temperature
  6. filtrationfiltered
  7. customthe solvent evaporated in vacuo
  8. dissolutionthe residue dissolved in 200 ml of dichloromethane
  9. washwashed successively with a 5% aqueous solution of sodium carbonate, 2×200 ml, 10% aqueous solution of citric acid, 2×200 ml
  10. customThe dichloromethane layer is separated
  11. dry with materialdried over sodium sulfate
  12. customevaporated in vacuo
  13. customthe residue purified by chromatography
  14. washeluting with dichloromethane-methanol (95:5)

Sources & evidence

ORD record
ord-5aba1407b884414e9c85af70123897b9
Source dataset
uspto-grants-1986_06
Patent number
US04596819

Reaction notes

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