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

HRID 245107Notes

Reaction equation

HRID 245107 reaction equation
[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([O:20][CH3:21])[N:17]=[C:16]([CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:27])[C:4]=1[OH:28])[CH3:2].[CH2:29]([C@@H:31]1[O:33][CH2:32]1)Cl>[OH-].[Na+].C(O)(C)C.CC(=O)OCC>[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([O:20][CH3:21])[N:17]=[C:16]([CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:27])[C:4]=1[O:28][CH2:29][C@@H:31]1[CH2:32][O:33]1)[CH3:2]

Participants

6

Reactant 2

HCID 2734062(-)-Epichlorohydrin2×HCID 1363910162-Ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenol

Product 1

HCID 866646314-[(2S)-3-(3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-2-(1-ethyl-propyl)-6-methoxy-pyridineYield 66.8%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 2-ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenol (355 mg, 931 μmol) and (R)-epichlorohydrine (861 mg, 9.31 mmol) in 3 M aq. NaOH (4 mL) and isopropanol (15 mL) is stirred at rt for 18 h before a second portion of (R)-epichlorohydrine (430 mg, 4.65 mmol) is added. Stirring is continued at rt for 8 h. The mixture is diluted with EA (100 mL) and washed twice with 1 N aq. NaOH solution (2×15 mL) followed by brine (25 mL). The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give 4-[(2S)-3-(3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-2-(1-ethyl-propyl)-6-methoxy-pyridine (272 mg) as a white powder; LC-MS: tR=1.25 min, [M+H]+=438.09.

Workup

  1. additionis added
  2. washwashed twice with 1 N aq. NaOH solution (2×15 mL)
  3. extractionextract
  4. dry with materialis dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-dd0276d6552140f5b27c8e588b76a33b
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

Loading…