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

HRID 1279850Notes

Reaction equation

HRID 1279850 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]([NH2:41])[CH2:37][CH2:38][O:39][CH3:40]>ClCCl>[CH:15]1([CH2:14][CH2:13][CH2:12][C@@H:8]([C:9]2[O:11][N:41]=[C:36]([CH2:37][CH2:38][O:39][CH3:40])[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 4390391(1E)-N'-Hydroxy-3-methoxypropanimidamide hydrochlorideHCID 9835906(2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid

Product 1

HCID 59909773tert-butyl (3R)-6-cyclohexyl-3-[3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl]hexanoateYield 63.4%

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′-carbonyidiimidazole (272 mg, 1.70 mmol) and the solution was stirred at room temperature for 1 hour. N′-hydroxy-3-methoxypropanimidamide (J.Amer.Chem.Soc.; 80; 1958; 3769-3771) (201 mg, 1.70 mmol) was then added and the mixture was stirred for 1 hour. 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 a colourless oil (410 mg).

Workup

  1. stirringthe mixture was stirred for 1 hour
  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-f449c9da092a4d1c9409de9eb9f105e1
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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