Dicyclohexylcarbodiimide → (2S)-phenylmethyl 2-[[1-[[(2-ethoxy-2-oxoethyl)amino]carbonyl]-3-methylbutoxy]methyl]-1-pyrrolidinecarboxylate

HRID 1982642Notes

Reaction equation

HRID 1982642 reaction equation
Cl.[NH2:2][CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:9]([CH:12]([O:17][CH2:18][C@@H:19]1[CH2:23][CH2:22][CH2:21][N:20]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])[CH2:13][CH:14]([CH3:16])[CH3:15])(O)=[O:10].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl.C(N(CC)CC)C>[CH2:7]([O:6][C:4](=[O:5])[CH2:3][NH:2][C:9]([CH:12]([O:17][CH2:18][C@@H:19]1[CH2:23][CH2:22][CH2:21][N:20]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[CH3:8]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2723640Glycine ethyl ester, hydrochlorideHCID 57212195(2S)-phenylmethyl 2-[(1-carboxy-3-methylbutoxy)methyl]-1-pyrrolidinecarboxylate

Product 1

HCID 57190339(2S)-phenylmethyl 2-[[1-[[(2-ethoxy-2-oxoethyl)amino]carbonyl]-3-methylbutoxy]methyl]-1-pyrrolidinecarboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Triethylamine, 1.15 g (0.0114 mol), is added to 1.59 g (0.0114 mol of ethyl glycinate hydrochloride in 200 ml of dichloromethane at 0°. To the previous suspension at 0° C. is added 4 g (0.0114 mol) of (2S)-phenylmethyl 2-[(1-carboxy-3-methylbutoxy)methyl]-1-pyrrolidinecarboxylate (center on side chain is R,S mixture), 1.74 g (0.0114 mol) of 1-hydroxybenzotriazole and 2.35 g (0.0114 mol) of dicyclohexylcarbodiimide. The mixture is allowed to reach room temperature and stirred 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 dichloromethanemethanol (98:2) to give (2S)-phenylmethyl 2-[[1-[[(2-ethoxy-2-oxoethyl)amino]carbonyl]-3-methylbutoxy]methyl]-1-pyrrolidinecarboxylate (center on side chain is R,S mixture), 4 g; [α]D25 -72.7° (c 0.33, methanol).

Workup

  1. customto reach room temperature
  2. filtrationfiltered
  3. customthe solvent evaporated in vacuo
  4. dissolutionthe residue dissolved in 200 ml of dichloromethane
  5. washwashed successively with a 5% aqueous solution of sodium carbonate, 2×200 ml, 10% aqueous solution of citric acid, 2×200 ml
  6. customThe dichloromethane layer is separated
  7. dry with materialdried over sodium sulfate
  8. customevaporated in vacuo
  9. customthe residue purified by chromatography
  10. washeluting with dichloromethanemethanol (98:2)

Sources & evidence

ORD record
ord-5db0922609214ca9ae317b2d6d472a7f
Source dataset
uspto-grants-1986_06
Patent number
US04596819

Reaction notes

Loading…