4-Methylmorpholine → (3R)-3-{3-[(2-Amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}-6-cyclohexyl-N-hydroxyhexanamide

HRID 1279795Notes

Reaction equation

HRID 1279795 reaction equation
[NH2:1][C:2](=[O:25])[CH2:3][O:4][CH2:5][C:6]1[N:10]=[C:9]([C@H:11]([CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:12][C:13](O)=[O:14])[O:8][N:7]=1.CN1CCOCC1.ClC(OCC(C)C)=O.C[Si](C)(C)[O:43][NH2:44]>O1CCCC1.CO>[NH2:1][C:2](=[O:25])[CH2:3][O:4][CH2:5][C:6]1[N:10]=[C:9]([C@H:11]([CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:12][C:13]([NH:44][OH:43])=[O:14])[O:8][N:7]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 59909790(3R)-3-{3-[(2-amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}6-cyclohexylhexanoic acid

Product 1

HCID 9947442(3R)-3-{3-[(2-Amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}-6-cyclohexyl-N-hydroxyhexanamideYield 32.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3R)-3-{3-[(2-amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}6-cyclohexylhexanoic acid (Preparation 91) (178 mg, 0.50 mmol) and N-methylmorpholine (1001 μl, 0.91 mmol) in anhydrous tetrahydrofuran (8 ml) was cooled to 0° C., treated with isobutyl chloroformate (70 μl, 0.54 mmol) and stirred under a nitrogen atmosphere for 2.5 hours. O-(Trimethylsilyl)hydroxylamine (200 μl, 1.63 mmol) was added and the mixture was stirred for 18 hours, being allowed to warm to room temperature over this time. The mixture was then treated with methanol and stirred at room temperature for 1 hour. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed with water and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The oil was purified by column chromatography on silica gel eluting with a gradient system of 98:2 (dichloromethane:methanol) gradually changing to 90:10 (dichloromethane:methanol) and then neat methanol to afford the title compound as a colourless oil (60 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. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe oil was purified by column chromatography on silica gel eluting with a gradient system of 98:2 (dichloromethane:methanol)

Sources & evidence

ORD record
ord-12f7431b81804a928e922d20ed1aaff4
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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