Hydrogen Peroxide → Tert-butyl 4-(hydroxymethyl)-2-phenylpiperidine-1-carboxylate

HRID 473797Notes

Reaction equation

HRID 473797 reaction equation
[CH2:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:3]1.B.[O:22]1CCCC1.[OH-].[Na+].OO>O1CCCC1.O>[OH:22][CH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:12])[CH3:13])=[O:9])[CH:4]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:3]1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 67505825Tert-butyl 4-methylene-2-phenylpiperidine-1-carboxylate

Product 1

HCID 67505826Tert-butyl 4-(hydroxymethyl)-2-phenylpiperidine-1-carboxylateYield 79.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To solution of tert-butyl 4-methylene-2-phenylpiperidine-1-carboxylate (2.20 g, 8.04 mmol) in tetrahydrofuran (50 mL) at 0° C. was added borane-tetrahydrofuran complex (1M solution in tetrahydrofuran) (12.1 mL, 12.1 mmol) and the reaction mixture was stirred at 0° C. for 1 hour. The reaction mixture was allowed to warm to room temperature then stirred for an additional 2 hours. It was cooled to 0° C. and 2M aqueous sodium hydroxide (8.0 mL, 16.0 mmol) was added slowly followed by the slow addition of 30% aqueous hydrogen peroxide (5.5 mL, 48.4 mmol). The mixture was stirred for another hour then diluted with water (100 mL) and partitioned with ethyl acetate (250 mL). The organic layer was separated and washed with 2M aqueous sodium thiosulfate (100 mL), brine, dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography in silica gel (chloroform:methanol 9:1 to 4:1) provided tert-butyl 4-(hydroxymethyl)-2-phenylpiperidine-1-carboxylate (1.86 g, 79%). 1H NMR (400 MHz, CDCl3): 7.30 (m, 2H), 7.20 (m, 3H), 4.86 (dd, 1H), 4.04 (m, 1H), 3.62 (m, 0.5H), 3.44 (m, 3H), 3.24 (m, 1H), 2.12 (m, 0.5H), 1.93 (m, 1H), 1.64 (m, 2H), 1.42 (m, 1H), 1.26 (s, 9H). GC/MS (EI) for C17H25NO3: 235 (M-tBu+).

Workup

  1. temperatureto warm to room temperature
  2. stirringthen stirred for an additional 2 hours
  3. temperatureIt was cooled to 0° C.
  4. stirringThe mixture was stirred for another hour
  5. custompartitioned with ethyl acetate (250 mL)
  6. customThe organic layer was separated
  7. washwashed with 2M aqueous sodium thiosulfate (100 mL), brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-ebb2eacd0a0f43218d9e1e65ab7229de
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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