Propylamine → (3R)-6-cyclohexyl-3-{3-[(propylamino)carbonyl]-1,2,4-oxadiazol-5-yl}hexanoic acid

HRID 1279818Notes

Reaction equation

[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([O:22]CC)=O)[N:16]=2)[CH2:11][C:12]([OH:14])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:25]([NH2:28])[CH2:26][CH3:27]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([NH:28][CH2:25][CH2:26][CH3:27])=[O:22])[N:16]=2)[CH2:11][C:12]([OH:14])=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

Conditions

Temperature: 125 °C

Procedure

A solution of (3R)-6-cyclohexyl-3-[3-(ethoxycarbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid (Preparation 4) (107 mg, 0.31 mmol) in toluene (2 ml) was treated with n-propylamine (250 μl, 3.10 mmol) and the mixture was heated at 125° C. in a sealed vessel for 2 hours. The mixture was cooled to room temperature, diluted with ethyl acetate and washed sequentially with aqueous citric acid solution (5% w/v), 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:ethyl acetate (80:20) gradually changing to dichloromethane:ethyl acetate (60:40) then to dichloromethane:methanol (90:10) to afford the title compound as an oil (76 mg).

Workup

temperatureThe mixture was cooled to room temperature
washwashed sequentially with aqueous citric acid solution (5% w/v), water and brine
dry with materialdried over anhydrous sodium sulphate
filtrationfiltered
customthe solvent removed under reduced pressure
customThe residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:ethyl acetate (80:20)

Sources & evidence

ORD record: ord-80f5249a7fe045fea479c9fd71b29b5a
Source dataset: uspto-grants-2002_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06448278B2

Reaction notes

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