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

HRID 2182927Notes

Reaction equation

HRID 2182927 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-19587c2d02d14a05942389aaf19c333d
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

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