Cesium carbonate → 2-(4-(5-(2-Cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)ethanol

HRID 2278779Notes

Reaction equation

HRID 2278779 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.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:36][CH2:37][OH:38]>CN(C=O)C.C([O-])(O)=O.[Na+]>[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][CH2:36][CH2:37][OH:38])=[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 3

HCID 10796Cesium carbonateHCID 108982-BromoethanolHCID 1363910154-[5-(2-Cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol

Product 1

HCID 705581362-(4-(5-(2-Cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)ethanolYield 45.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °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 (1.26 g, 3.32 mmol) in DMF (20 mL), Cs2CO3 (6.49 g, 19.9 mmol) is added. The mixture is stirred at rt for 10 min before 2-bromoethanol (2.07 g, 16.6 mmol) is added. The mixture is stirred at 60° C. for 5 days. The mixture is cooled to rt, diluted with sat. aq. NaHCO3 solution (50 mL) and extracted twice with EA (2×200 mL). The org. extracts are combined and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)ethanol (639 mg) as a pale yellow oil; 1H NMR (CDCl3): δ: 7.90 (s, 1H), 7.88 (s, 1H), 7.51 (s, 1H), 7.31 (s, 1H), 4.02 (s, 3H), 3.97-4.01 (m, 4H), 3.21-3.29 (m, 1H), 2.79 (q, J=7.6 Hz, 2H), 2.42 (s, 3H), 2.15 (t, J=5.5 Hz, 1H), 2.06-2.14 (m, 2H), 1.83-1.95 (m, 4H), 1.68-1.80 (m, 2H), 1.33 (t, J=7.6 Hz, 3H).

Workup

  1. additionis added
  2. temperatureThe mixture is cooled to rt
  3. extractionextracted twice with EA (2×200 mL)
  4. concentrationconcentrated
  5. customThe crude product is purified by CC on silica gel eluting with heptane:EA 4:1

Sources & evidence

ORD record
ord-722ae29f5eed4f89ab68c655ed40877a
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

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