Hydrogen Peroxide → HCID 59177814, compound

HRID 423662Notes

Reaction equation

HRID 423662 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[N:15]=[CH:14][C:13]([O:16][CH2:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)=[CH:12][CH:11]=1.OO.[O-:32]S([O-])=O.[Na+].[Na+].CCOC(C)=O.FC(F)(F)[CH:46]([OH:51])[C:47]([F:50])([F:49])[F:48]>>[C:46]([OH:51])([C:47]([F:50])([F:49])[F:48])=[O:16].[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:9])=[O:32])[CH:5]=[CH:4][C:3]=1[C:10]1[N:15]=[CH:14][C:13]([O:16][CH2:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)=[CH:12][CH:11]=1

Participants

7

Reactant 5

HCID 784Hydrogen PeroxideHCID 8857Ethyl AcetateHCID 135291,1,1,3,3,3-Hexafluoro-2-propanolHCID 24437Sodium SulfiteHCID 66673094HCID 66673094, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 59177814HCID 59177814, compoundYield 48%

Procedure

A mixture of 1-methylethyl 4-[({6-[2-fluoro-4-(methylthio)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (50 mg, 0.12 mmol) in 1,1,1,3,3,3-hexafluoro-2-propanol (2 mL) was treated with 30% aqueous H2O2 (0.027 mL, 0.24 mmol) at ambient temperature. After 2 h, saturated aqueous Na2SO3 (5 mL) was added carefully and the mixture was stirred for 10 min. EtOAc (3 mL) was added, the organic layer was separated and dried over Na2SO4 and the solvent evaporated off. The crude product was purified by reverse-phase preparative HPLC using a CH3CN:H2O gradient (10:90 to 100:0) with 0.1% TFA as a modifier to give 25 mg (48%) of the title compound as a white solid. 1HNMR (400 MHz, CDCl3): δ 8.41 (d, 1H, J=2.7 Hz), 8.14 (t, 1H, J=7.8 Hz), 7.78 (dd, 1H, Ja=8.7 Hz, Jb=1.5 Hz), 7.51 (dd, 1H, Ja=10.5 Hz, Jb=1.4 Hz), 7.44 (dd, 1H, Ja=8.2 Hz, Jb=1.5 Hz), 7.30-7.23 (m, 1H), 4.92 (septet, 1H, J=6.2 Hz), 4.30-4.15 (m, 2H), 3.90 (d, 2H, J=6.4 Hz), 2.85-2.74 (m, 2H), 2.76 (s, 3H), 2.06-1.96 (m, 1H), 1.85 (m, 2H), 1.88-1.22 (m, 2H), 1.24 (d, 6H, J=6.4 Hz); LRMS (ESI), m/z 435 (M+H).

Workup

  1. customthe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. customthe solvent evaporated off
  4. customThe crude product was purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-19ba90e26ebf4e2bb3697f9a835c4af3
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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