Isopropanol → tert-Butyl 3-(4-(5-(5-chloro-6-isopropoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate

HRID 1820990Notes

Reaction equation

HRID 1820990 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:16][C:15]=3[CH3:29])[N:10]=2)[CH:5]=[N:6][C:7]=1Cl.[CH3:30][CH:31]([OH:33])[CH3:32].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:16][C:15]=3[CH3:29])[N:10]=2)[CH:5]=[N:6][C:7]=1[O:33][CH:31]([CH3:32])[CH3:30]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 86623617Tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate

Product 1

HCID 68892122tert-Butyl 3-(4-(5-(5-chloro-6-isopropoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoateYield 72.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 138 mg (0.32 mmol) of tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate and 36.5 μL (0.48 mmol) of 2-propanol in 10 mL of THF was added 477 μL (0.48 mmol) of sodium bis(trimethylsilyl)amide (1.0 M in THF). The mixture was refluxed overnight, cooled to rt and concentrated. Chromatography on a Biotage 40S cartridge using 1:19 v/v EtOAc/hexanes as the eluant gave 106 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.43 (s, 9H), 1.44 (d, J=6.2, 6H), 2.58 (t, J=7.8, 2H), 2.65 (s, 3H), 2.95 (t, J=7.7, 2H), 5.49 (m, 1H), 7.17-7.18 (m, 2H), 8.00 (d, J=8.4, 1H), 8.38 (d, J=2.0, 1H), 8.86 (d, J=2.3, 1H).

Workup

  1. temperatureThe mixture was refluxed overnight
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-51b18b4a379c495f88790598232a5ed7
Source dataset
uspto-grants-2009_10
Patent number
US07605171B2

Reaction notes

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