(-)-Epichlorohydrin → (S)-5-(2-cyclopentyl-6-methoxypyridin-4-yl)-3-(3-ethyl-5-methyl-4-(oxiran-2-ylmethoxy)phenyl)-1,2,4-oxadiazole

HRID 2278782Notes

Reaction equation

HRID 2278782 reaction equation
[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][N:15]=[C:14]([C:17]4[CH:22]=[C:21]([CH3:23])[C:20]([OH:24])=[C:19]([CH2:25][CH3:26])[CH:18]=4)[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>CC(O)C.[OH-].[Na+].CC(=O)OCC>[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][N:15]=[C:14]([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)[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 1363910154-[5-(2-Cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol

Product 1

HCID 86702019(S)-5-(2-cyclopentyl-6-methoxypyridin-4-yl)-3-(3-ethyl-5-methyl-4-(oxiran-2-ylmethoxy)phenyl)-1,2,4-oxadiazoleYield 95.4%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (2.32 g, 4.91 mmol) in 2-propanol (60 mL) and 3 N aq. NaOH (6 mL), (R)-epichlorohydrine (4.55 g, 49.1 mmol) is added. The mixture is stirred at 45° C. for 6 h before it is diluted with EA (100 mL) and washed twice with 1 N aq. NaOH (2×15 mL) followed by brine (25 mL). The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by MPLC on silica gel eluting with heptane:EA 1:1 to give (S)-5-(2-cyclopentyl-6-methoxypyridin-4-yl)-3-(3-ethyl-5-methyl-4-(oxiran-2-ylmethoxy)phenyl)-1,2,4-oxadiazole (2.04 g) as a colourless wax; LC-MS: tR=1.52 min, [M+H]+=436.11; 1H NMR (CDCl3): δ 7.88-7.90 (m, 1H), 7.85-7.88 (m, 1H), 7.51 (d, J=1.1 Hz, 1H), 7.31 (d, J=1.2 Hz, 1H), 4.14 (dd, J1=11.1 Hz, J2=3.1 Hz, 1H), 4.02 (s, 3H), 3.83 (dd, J1=11.1 Hz, J2=6.0 Hz, 1H), 3.40-3.44 (m, 1H), 3.19-3.29 (m, 1H), 2.94 (dd, J1=4.9 Hz, J2=4.3 Hz, 1H), 2.75-2.83 (m, 3H), 2.41 (s, 3H), 2.06-2.16 (m, 2H), 1.84-1.94 (m, 4H), 1.70-1.79 (m, 2H), 1.33 (t, J=7.5 Hz, 3H).

Workup

  1. washwashed twice with 1 N aq. NaOH (2×15 mL)
  2. extractionextract
  3. dry with materialis dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by MPLC on silica gel eluting with heptane:EA 1:1

Sources & evidence

ORD record
ord-2c37c37ddcd8475890d08d4b1bdaf1c9
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

Loading…