Hydrogen Peroxide → HCID 57546233, compound

HRID 913956Notes

Reaction equation

HRID 913956 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:12]=[CH2:13])[C:8]2[C:4](=[CH:5][N:6]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:7]=2)[CH:3]=1.[O:44]1CCCC1.B.C1COCC1.OO.[OH-].[Na+]>CCOCC>[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:18][CH2:17]2)[CH2:12][CH2:13][OH:44])[C:8]2[C:4](=[CH:5][N:6]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:7]=2)[CH:3]=1

Participants

7

Reactant 5

HCID 784Hydrogen PeroxideHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 57546195HCID 57546195, compound

Product 1

HCID 57546233HCID 57546233, compoundYield 70.7%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)allyloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (84 mg, 0.133 mmol) in tetrahydrofuran (2 mL, 0.133 mmol) at 0 C was added Borane-THF (0.267 mL, 0.267 mmol). The reaction was allowed to slowly warm to room temperature over 1.5 h. The reaction was recooled to 0 C and treated with hydrogen peroxide (30%) (1.3 mL, 0.133 mmol) followed by sodium hydroxide (0.6 mL, 2.400 mmol). After stirring for 30 min, the reaction was diluted with ether and quenched by addition of sat'd ammonium chloride. The mixture was extracted with ether, washed with brine, dried over magnesium sulfate, filtered and concentrated. It was purified by column chromatography (30% to 47% EtOAc/Hex) to give title compound (61 mg, 0.094 mmol, 70.6% yield) as white foam solid. 1H-NMR (CDCl3, 500 MHz) δ 8.02 (s, 1H), 7.52 (d, J=1.5 Hz, 1H), 7.30 (m, 2H), 7.06 (t, J=8.8 Hz, 2H), 6.70 (bs, 1H), 5.64 (AB, Δν=17.1 Hz, J=10.7 Hz, 2H), 5.07 (t, J=6.7 Hz, 1H), 3.75 (m, 2H), 3.57 (m 2H), 3.38 (m, 2H), 2.95-3.25 (m, 2H), 2.05-2.25 (m, 2H), 1.85 (m, 2H), 1.43 (s, 9H), 0.90 (t, J=8.5 Hz, 2H), −0.06 (s, 9H). LC/MS (HPLC method 3): tR=4.29 min, 648.2(MH)+.

Workup

  1. customquenched by addition of sat'd ammonium chloride
  2. extractionThe mixture was extracted with ether
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customIt was purified by column chromatography (30% to 47% EtOAc/Hex)

Sources & evidence

ORD record
ord-89fbb68a0d8b4c5aaae8982c859f318b
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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