4-Methylmorpholine → Ethyl 3-(5-{(1R)-4-cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazol-3-yl)propanoate

HRID 2182948Notes

Reaction equation

HRID 2182948 reaction equation
NC(=O)CO[CH2:5][C:6]1[N:10]=[C:9]([C@H:11]([CH2:17][CH2:18][CH2:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:12][C:13]([NH:15][OH:16])=[O:14])[O:8][N:7]=1.C1(CCCC(C2ON=C(C[CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49])N=2)CC(O)=O)CCCCC1.CN1CCOCC1.ClC(OCC(C)C)=O.C[Si](C)(C)ON>O1CCCC1.CO>[CH:20]1([CH2:19][CH2:18][CH2:17][C@@H:11]([C:9]2[O:8][N:7]=[C:6]([CH2:5][CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49])[N:10]=2)[CH2:12][C:13]([NH:15][OH:16])=[O:14])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 9947442(3R)-3-{3-[(2-Amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}-6-cyclohexyl-N-hydroxyhexanamideHCID 224807616-Cyclohexyl-3-[3-(3-ethoxy-3-oxopropyl)-1,2,4-oxadiazol-5-yl]hexanoic acid

Product 1

HCID 10156678Ethyl 3-(5-{(1R)-4-cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazol-3-yl)propanoate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3R)-6-cyclohexyl-3-[3-(3-ethoxy-3-oxopropyl)-1,2,4-oxadiazol-5-yl]hexanoic acid (Preparation 94) (110 mg, 0.30 mmol) and N-methylmorpholine (60 μl, 0.54 mmol) in anhydrous tetrahydrofuran (6 ml) was cooled to 0° C., treated with isobutyl chloroformate (42 μl, 0.32 mmol) and stirred under a nitrogen atmosphere for 2.5 hours. O-(Trimethylsilyl)hydroxylamine (120 μl, 1.00 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 3 hours. 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 100:0 (dichloromethane:methanol) gradually changing to 90:10 (dichloromethane:methanol) to afford the title compound as a yellow oil (94 mg).

Workup

  1. stirringthe mixture was stirred for 18 hours
  2. stirringstirred at room temperature for 3 hours
  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 100:0 (dichloromethane:methanol)

Sources & evidence

ORD record
ord-d4584e0f184b47ff80a91161533c572d
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

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