Hydrogen Peroxide → (+/-)-5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridine

HRID 423669Notes

Reaction equation

HRID 423669 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][O:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]4[CH:28]=[CH:27][C:26]([S:29][CH3:30])=[CH:25][CH:24]=4)=[N:21][CH:22]=3)[CH2:11][CH2:10]2)[O:6][N:5]=1)[CH3:3].[OH:31]O>FC(F)(F)C(O)C(F)(F)F.C(Cl)Cl>[CH3:3][CH:2]([C:4]1[N:8]=[C:7]([N:9]2[CH2:10][CH2:11][CH:12]([CH2:15][O:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]4[CH:24]=[CH:25][C:26]([S:29]([CH3:30])=[O:31])=[CH:27][CH:28]=4)=[N:21][CH:22]=3)[CH2:13][CH2:14]2)[O:6][N:5]=1)[CH3:1]

Participants

5

Reactant 2

HCID 784Hydrogen PeroxideHCID 666736235-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylthio)phenyl]pyridine

Product 1

HCID 46861617(+/-)-5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylsulfinyl)phenyl]pyridineYield 86%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 135291,1,1,3,3,3-Hexafluoro-2-propanolSolvent

Conditions

Temperature
8 °C

Procedure

A solution of 5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylthio)phenyl]pyridine (93.7 g, 221 mol) in 1,1,1,3,3,3-hexafluoro-2-propanol (300 mL) at 5° C. was treated with 30% aqueous H2O2 (29 mL, 287 mol) over a 1.5 h period at such a rate to maintain temperature between approximately 6-10° C. The reaction was stirred at 5° C. for 2.5 h. The reaction was diluted with CH2Cl2 (600 mL), quenched by the addition of saturated aqueous Na2SO3 (400 mL), allowed to warm to room temperature and stirred for 30 min. The organic layer was washed with saturated aqueous Na2SO3 (400 mL×2), brine and was dried over MgSO4 and concentrated to give a tan solid. The solid was recrystallized from MeOH to provide the title compound (83.5 g, 86%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.37 (d, 1H, J=2.7 Hz), 8.07 (d, 2H, J=8.4 Hz), 7.74-7.64 (m, 3H), 7.27 (dd, 1H, Ja=8.7 Hz, Jb=2.8 Hz), 4.30-4.15 (m, 2H), 3.92 (d, 2H, J=6.2 Hz), 3.20-3.05 (m, 2H), 2.87 (septet, 1H, J=6.9 Hz), 2.74 (s, 3H), 2.19-2.01 (m, 1H), 2.00-1.90 (m, 2H), 1.55-1.40 (m, 2H), 1.27 (d, 6H, J=7.0 Hz); LRMS (ESI), m/z 441 (M+H).

Workup

  1. customquenched by the addition of saturated aqueous Na2SO3 (400 mL)
  2. temperatureto warm to room temperature
  3. stirringstirred for 30 min
  4. washThe organic layer was washed with saturated aqueous Na2SO3 (400 mL×2), brine
  5. dry with materialwas dried over MgSO4
  6. concentrationconcentrated
  7. customto give a tan solid
  8. customThe solid was recrystallized from MeOH

Sources & evidence

ORD record
ord-6c63daf8ec55434abe442dfe2588b863
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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