Hydrogen Peroxide → HCID 58993659, compound

HRID 391442Notes

Reaction equation

HRID 391442 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:15][O:16][CH2:17][C:18]2([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[CH:7]=1.C([Li])CCC.C[O:43]B(OC)OC.[OH-].[Na+].OO.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[F:14][C:11]1[CH:10]=[CH:9][C:8]([C:6]2[CH:7]=[C:2]([OH:43])[CH:3]=[C:4]([CH2:15][O:16][CH2:17][C:18]3([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:22][CH2:23]3)[CH:5]=2)=[CH:13][CH:12]=1

Participants

9

Reactant 6

HCID 784Hydrogen PeroxideHCID 8470Trimethyl borateHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 58993666HCID 58993666, compoundHCID 178418339Butyllithium

Product 1

HCID 58993659HCID 58993659, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 4-(((5-bromo-4′-fluorobiphenyl-3-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (0.47 g, 0.85 mmol) was dissolved in dry tetrahydrofuran (5 mL) and stirred at room temperature for 15 min. The stirred mixture was cooled to −78° C. and treated with a solution of n-butyllithium (1.6 M in hexanes, 0.61 mL, 0.98 mmol) over several minutes. After 30 min, the mixture was treated with trimethylborate (0.28 mL, 2.55 mmol). The reaction mixture was stirred at 78° C. for 1 h, then allowed to warm to room temperature over several hours. The mixture was cooled to 0° C. and treated with a 10 N sodium hydroxide solution (60 μL) and hydrogen peroxide (30% in water, 0.44 mL, 3.9 mmol). The reaction was warmed to room temperature over several hours and then treated with saturated ammonium chloride. The reaction was diluted with ethyl acetate. The layers were separated and the organic layer washed with brine (2×), dried over sodium sulfate, filtered, and concentrated. Flash chromatography on silica gel (30% ethyl acetate/hexanes) afforded 280 mg (67%). 1H-NMR (CDCl3, 500 MHz) δ 7.38-7.43 (m, 2H), 7.19-7.35 (m, 5H), 7.02-7.09 (m, 2H), 6.86-6.88 (m, 1H), 6.79 (s, 1H), 6.46 (s, 1H), 4.33 (s, 2H), 3.70-3.74 (m, 2H), 3.38 (s, 2H), 2.98-3.07 (m, 2H), 2.13-2.17 (m, 2H), 1.83-1.92 (m, 2H), 1.41 (s, 9H). Mass spec.: 492.41 (MH)+.

Workup

  1. temperatureThe stirred mixture was cooled to −78° C.
  2. waitAfter 30 min
  3. stirringThe reaction mixture was stirred at 78° C. for 1 h
  4. temperatureto warm to room temperature over several hours
  5. temperatureThe mixture was cooled to 0° C.
  6. temperatureThe reaction was warmed to room temperature over several hours
  7. customThe layers were separated
  8. washthe organic layer washed with brine (2×)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customFlash chromatography on silica gel (30% ethyl acetate/hexanes) afforded 280 mg (67%)

Sources & evidence

ORD record
ord-c37f7be0f6a14867a34860f8c6017aac
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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