Piconol → tert-butyl (3R)-6-cyclohexyl-3-(3-{[methyl(2-pyridinylmethyl)amino]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoate

HRID 1279836Notes

Reaction equation

[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([C:24]([NH:26][CH3:27])=[O:25])[N:20]=2)[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(P(CCCC)CCCC)CCC.O[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=1>C1(C)C=CC=CC=1>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([C:24]([N:26]([CH3:27])[CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=3)=[O:25])[N:20]=2)[CH2:11][C:12]([O:14][C:15]([CH3:17])([CH3:18])[CH3:16])=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

Conditions

Temperature: 0 °C

Procedure

1-1′-Azobis(N,N-dimethylformamide) (645 mg, 3.75 mmol) was added to a cooled solution of tert-butyl (3R)-6-cyclohexyl-3-{3-[(methylamino)carbonyl]-1,2,4-oxadiazol-5-yl}hexanoate (Preparation 7) (1.42 g, 3.75 mmol), tributylphosphine (930 μl, 3.75 mmol) and 2-hydroxymethylpyridine (240 μl, 2.50 mmol) in toluene (10 ml) and the resulting mixture was stirred at 0° C. under a nitrogen atmosphere for 15 minutes, then at room temperature for 72 hours. The mixture was filtered and the solvent removed from the filtrate under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of hexane:ethyl acetate (90:10) gradually changing to hexane:ethyl acetate (50:50) to afford the title compound as a pale yellow oil (530 mg).

Workup

waitat room temperature for 72 hours
filtrationThe mixture was filtered
customthe solvent removed from the filtrate under reduced pressure
customThe residue was purified by column chromatography on silica gel eluting with a gradient system of hexane:ethyl acetate (90:10)

Sources & evidence

ORD record: ord-7299dcba9dfb4fb0937598e5916210b2
Source dataset: uspto-grants-2002_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06448278B2

Reaction notes

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