Triethylamine → tert-Butyl (3R)-6-cyclohexyl-3-(3-{[3-(4-morpholinyl)-1-azetidinyl]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoate

HRID 1279829Notes

Reaction equation

HRID 1279829 reaction equation
[C:1]([O:5][C:6](=[O:28])[CH2:7][C@H:8]([C:18]1[O:22][N:21]=[C:20]([C:23](OCC)=[O:24])[N:19]=1)[CH2:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[NH:31]1[CH2:34][CH:33]([N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[CH2:32]1.C(N(CC)CC)C>C(O)C>[CH:12]1([CH2:11][CH2:10][CH2:9][C@@H:8]([C:18]2[O:22][N:21]=[C:20]([C:23]([N:31]3[CH2:34][CH:33]([N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[CH2:32]3)=[O:24])[N:19]=2)[CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:28])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 220613264-(Azetidin-3-yl)morpholine dihydrochlorideHCID 59909797ethyl 5-{(1R)-1-[2-(tert-butoxy)-2-oxoethyl]4-cyclohexylbutyl}-1,2,4-oxadiazole-3-carboxylate

Product 1

HCID 59909782tert-Butyl (3R)-6-cyclohexyl-3-(3-{[3-(4-morpholinyl)-1-azetidinyl]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoateYield 105.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of ethyl 5-{(1R)-1 -[2-(tert-butoxy)-2-oxoethyl]-4-cyclohexylbutyl}-1,2,4-oxadiazole-3-carboxylate (Preparation 3) (1.00 g, 2.54 mmol) in ethanol (10 ml) was treated with 4-(3-azetidinyl)morpholine dihydrochloride (2.72 g, 12.6 mmol) and triethylamine (2.56 g, 25 mmol) and the resulting mixture was heated under reflux under a nitrogen atmosphere for 24 hours. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed sequentially with water and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (97:3) gradually changing to dichloromethane:methanol (95:5) to afford the title compound as a colourless oil (1.32 g).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux under a nitrogen atmosphere for 24 hours
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was partitioned between ethyl acetate and water
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic layers were washed sequentially with water and brine
  8. dry with materialdried over anhydrous sodium sulphate
  9. filtrationfiltered
  10. customthe solvent removed under reduced pressure
  11. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (97:3)

Sources & evidence

ORD record
ord-e6c487d7eb364866a64fb8b9f136a6d2
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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