1,1'-Carbonyldiimidazole → tert-Butyl (3R)-6-cyclohexyl-3-{3-(2-oxo-2-(1-pyrrolidinyl)ethyl]-1,2,4-oxadiazol-5-yl}hexanoate

HRID 2183014Notes

Reaction equation

HRID 2183014 reaction equation
[C:1]([O:5][C:6](=[O:21])[CH2:7][C@@H:8]([CH2:12][CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:9]([OH:11])=O)([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.O[N:35]=[C:36]([NH2:45])[CH2:37][C:38](=[O:44])[N:39]1[CH2:43][CH2:42][CH2:41][CH2:40]1>ClCCl>[CH:15]1([CH2:14][CH2:13][CH2:12][C@@H:8]([C:9]2[O:11][N:45]=[C:36]([CH2:37][C:38](=[O:44])[N:39]3[CH2:43][CH2:42][CH2:41][CH2:40]3)[N:35]=2)[CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:21])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 2803610N'-hydroxy-3-oxo-3-pyrrolidin-1-ylpropanimidamideHCID 9835906(2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid

Product 1

HCID 59909778tert-Butyl (3R)-6-cyclohexyl-3-{3-(2-oxo-2-(1-pyrrolidinyl)ethyl]-1,2,4-oxadiazol-5-yl}hexanoateYield 41.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid (Preparation 1) (500 mg, 1.70 mmol) in dichloromethane (30 ml) was treated with 1,1′-carbonyldiimidazole (272 mg, 1.70 mmol) and the solution was stirred at room temperature for 1 hour. N′-hydroxy-3-oxo-3-(1-pyrrolidinyl)propanimidamide (Patent FR 73-36858 731016) (291 mg, 1.70 mmol) was then added and the mixture was stirred for 17 hours. The solvent was removed under reduced pressure and the residue was heated neat at 110° C. under a nitrogen atmosphere for 2 hours. The crude product was then purified by column chromatography on silica gel eluting with dichloromethane:methanol (99:1) to afford the title compound as a colourless oil (309 mg).

Workup

  1. stirringthe mixture was stirred for 17 hours
  2. customThe solvent was removed under reduced pressure
  3. temperaturethe residue was heated neat at 110° C. under a nitrogen atmosphere for 2 hours
  4. customThe crude product was then purified by column chromatography on silica gel eluting with dichloromethane:methanol (99:1)

Sources & evidence

ORD record
ord-8155c805b92c4101a33f7367aab34bed
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

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