(-)-Epichlorohydrin → 2-cyclopentyl-4-[5-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-6-methoxy-pyridine

HRID 245119Notes

Reaction equation

HRID 245119 reaction equation
[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[N:16]=[C:15]([C:17]4[CH:22]=[C:21]([CH3:23])[C:20]([OH:24])=[C:19]([CH2:25][CH3:26])[CH:18]=4)[O:14][N:13]=3)[CH:9]=[C:8]([O:27][CH3:28])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:29]([C@@H:31]1[O:33][CH2:32]1)Cl>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[N:16]=[C:15]([C:17]4[CH:22]=[C:21]([CH3:23])[C:20]([O:24][CH2:29][C@@H:31]5[CH2:32][O:33]5)=[C:19]([CH2:25][CH3:26])[CH:18]=4)[O:14][N:13]=3)[CH:9]=[C:8]([O:27][CH3:28])[N:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 2

HCID 2734062(-)-EpichlorohydrinHCID 1363910174-[3-(2-Cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenol

Product 1

HCID 866646322-cyclopentyl-4-[5-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-6-methoxy-pyridineYield 55.8%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 4-[3-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenol (150 mg, 395 μmol) and (R)-epichlorohydrine (366 mg, 3.95 mmol) in isopropanol (4 mL) and 3 N aq. NaOH (1 mL) is stirred at rt for 72 h. The mixture is diluted with EA (50 mL), washed with 1 M aq. NaOH solution (20 mL) followed by brine (20 mL), dried over MgSO4, filtered and concentrated. The crude product is purified on prep. TLC plates using heptane:EA 1:1 to give 2-cyclopentyl-4-[5-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-6-methoxy-pyridine (96 mg) as a pale yellow oil; LC-MS**: tR=1.02 min, [M+H]+=436.18.

Workup

  1. washwashed with 1 M aq. NaOH solution (20 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product is purified on prep

Sources & evidence

ORD record
ord-1f8b676237374a119cbbe48f1b6cb76e
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

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