1,1'-Carbonyldiimidazole → (3R)-6-cyclohexyl-N-hydroxy-3-[3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl]hexanamide

HRID 1279781Notes

Reaction equation

HRID 1279781 reaction equation
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([CH2:20][CH2:21][O:22][CH3:23])[N:16]=2)[CH2:11][C:12](O)=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:37][OH:38]>O1CCCC1>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([CH2:20][CH2:21][O:22][CH3:23])[N:16]=2)[CH2:11][C:12]([NH:37][OH:38])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 443297Hydroxyamine hydrochlorideHCID 59909767(3R)-6-cyclohexyl-3-[3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid

Product 1

HCID 10268788(3R)-6-cyclohexyl-N-hydroxy-3-[3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl]hexanamideYield 38.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of ((3R)-6-cyclohexyl-3-[3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid (Preparation 51) (245 mg, 0.76 mmol) in anhydrous tetrahydrofuran (10 ml) was treated with 1,1′-carbonyldiimidazole (123 mg, 0.76 mmol) and the mixture stirred at room temperature under a nitrogen atmosphere for 1 hour. Hydroxylamine hydrochloride (53 mg, 0.76 mmol) was then added and the mixture stirred for 18 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:0.88 ammonia (95:5:0.5). The residue was dissolved in ethyl acetate, washed with hydrochloric acid (1M), dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure to afford the title compound as an oil (100 mg)

Workup

  1. stirringthe mixture stirred for 18 hours
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was purified by column chromatography on silica gel eluting with dichloromethane
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with hydrochloric acid (1M)
  6. dry with materialdried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-b15b2945042844a9988901d123605725
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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