Methanol → (3R)-6-cyclohexyl-N-hydroxy-3-[3-(1H-imidazol-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanamide

HRID 2182953Notes

Reaction equation

HRID 2182953 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][C:21]3[NH:22][CH:23]=[CH:24][N:25]=3)[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.C[Si](C)(C)[O:40][NH2:41].CO>O1CCCC1>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([CH2:20][C:21]3[NH:22][CH:23]=[CH:24][N:25]=3)[N:16]=2)[CH2:11][C:12]([NH:41][OH:40])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 887MethanolHCID 682631,1'-CarbonyldiimidazoleHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 59909753(3R)-6-cyclohexyl-3-[3-(1H-imidazol-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid

Product 1

HCID 59909768(3R)-6-cyclohexyl-N-hydroxy-3-[3-(1H-imidazol-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanamideYield 31.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3R)-6-cyclohexyl-3-[3-(1H-imidazol-2-ylmethyl)-1,2,4-oxadiazol-5-yl]hexanoic acid (Preparation 103) (200 mg, 0.43 mmol) in anhydrous tetrahydrofuran (5 ml) was treated with 1,1′-carbonyldiimidazole (77 mg, 0.48 mmol) and stirred under a nitrogen atmosphere for 30 minutes. O-(Trimethylsilyl)hydroxylamine (160 μl, 1.30 mmol) was added and the mixture was stirred for 18 hours. The mixture was then treated with methanol (4 ml) and stirred at room temperature for 1 hour. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with 90:10:1 (dichloromethane:methanol:ammonia) to afford a colourless oil which began to crystallise once a little methanol and dichloromethane were added. The solid was triturated with dichloromethane and dried under reduced pressure to afford the title compound as a solid (49 mg).

Workup

  1. stirringthe mixture was stirred for 18 hours
  2. stirringstirred at room temperature for 1 hour
  3. customThe solvent was removed under reduced pressure
  4. customThe residue was purified by column chromatography on silica gel eluting with 90:10:1 (dichloromethane:methanol:ammonia)
  5. customto afford a colourless oil which
  6. customto crystallise once a little methanol and dichloromethane
  7. additionwere added
  8. customThe solid was triturated with dichloromethane
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-bac51e86eb3348089c89696b48540d47
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

Loading…