1,1'-Carbonyldiimidazole → tert-butyl (3R)-6-cyclohexyl-3-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]hexanoate

HRID 1279848Notes

Reaction equation

HRID 1279848 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]([NH2:40])[CH2:37][O:38][CH3:39]>ClCCl>[CH:15]1([CH2:14][CH2:13][CH2:12][C@@H:8]([C:9]2[O:11][N:40]=[C:36]([CH2:37][O:38][CH3:39])[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 4126736N'-hydroxy-2-methoxyethanimidamideHCID 9835906(2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid

Product 1

HCID 59909823tert-butyl (3R)-6-cyclohexyl-3-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]hexanoateYield 56.2%

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 mol) and the solution was stirred at room temperature for 1 hour. The N′-hydroxy-2-methoxyethanimidamide (J.Med.Chem,; 40; 8; 1997; 1230-1246) (177 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 120° 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 an oil (350 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 120° 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-459a520398f04835ace2fe80702cec9f
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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