1,1'-Carbonyldiimidazole → 5-((4-Chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-3-oxo-pentanoic acid ethyl ester

HRID 408608Notes

Reaction equation

HRID 408608 reaction equation
[CH:1]1N=CN(C(N2C=NC=C2)=O)[CH:2]=1.[Cl:13][C:14]1[CH:44]=[CH:43][C:17]([CH2:18][N:19]([C:25]([C:27]2([CH3:42])[CH2:30][CH2:29][N:28]2[C:31](=[O:41])[CH2:32][C:33]2[CH:38]=[C:37]([CH3:39])[CH:36]=[C:35]([CH3:40])[CH:34]=2)=[O:26])[CH2:20][CH2:21]C(O)=O)=[CH:16][CH:15]=1.[Mg+2].[Cl-].[Cl-].[C:48]([OH:54])(=O)[CH2:49][C:50]([OH:52])=[O:51].C([K])C>C1COCC1>[CH2:1]([O:52][C:50](=[O:51])[CH2:49][C:48](=[O:54])[CH2:21][CH2:20][N:19]([CH2:18][C:17]1[CH:16]=[CH:15][C:14]([Cl:13])=[CH:44][CH:43]=1)[C:25]([C:27]1([CH3:42])[CH2:30][CH2:29][N:28]1[C:31](=[O:41])[CH2:32][C:33]1[CH:38]=[C:37]([CH3:39])[CH:36]=[C:35]([CH3:40])[CH:34]=1)=[O:26])[CH3:2]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 5360315Magnesium ChlorideHCID 705587863-((4-Chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-propionic acidHCID 178461627HCID 178461627, compound

Product 1

HCID 705577355-((4-Chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-3-oxo-pentanoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of CDI (4 eq) in THF was added 3-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-propionic acid, compound 65 (1 eq.), the mixture was stirred for 4 h at 20° C., then MgCl2 (4 eq.) and ethyl potassium malonate (5 eq.) were added. The reaction was stirred for 15 h at 20° C. The crude was concentrated under reduced pressure then partitioned between water and EtOAc. The layers were separated and the organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with Hept/EtOAc/DCM/MeOH: 50/50/95/5 then 50/50/90/10) to afford 5-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-3-oxo-pentanoic acid ethyl ester.

Workup

  1. stirringThe reaction was stirred for 15 h at 20° C
  2. concentrationThe crude was concentrated under reduced pressure
  3. customthen partitioned between water and EtOAc
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude was purified by chromatography on silica gel (
  9. washelution with Hept/EtOAc/DCM/MeOH

Sources & evidence

ORD record
ord-a643370e2dc049998919e3d2296cd8b5
Source dataset
uspto-grants-2014_06
Patent number
US08759334B2

Reaction notes

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