Sodium Hydroxide → tert-Butyl 4-((3-amino-5-bromobenzyloxy)methyl)-4-phenylpiperidine-1-carboxylate

HRID 391453Notes

Reaction equation

HRID 391453 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:27]=[C:28]([N+:30]([O-])=O)[CH:29]=1)[CH2:5][O:6][CH2:7][C:8]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.O.O.[Sn](Cl)Cl.C(=O)(OC(C)(C)C)OC(C)(C)C.[OH-].[Na+]>C(OCC)(=O)C>[NH2:30][C:28]1[CH:27]=[C:4]([CH:3]=[C:2]([Br:1])[CH:29]=1)[CH2:5][O:6][CH2:7][C:8]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:15])[CH2:12][CH2:13]1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 61436Stannous chloride dihydrateHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) esterHCID 58993455tert-Butyl 4-((3-bromo-5-nitrobenzyloxy)methyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 58993695tert-Butyl 4-((3-amino-5-bromobenzyloxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent3×

Procedure

tert-Butyl 4-((3-bromo-5-nitrobenzyloxy)methyl)-4-phenylpiperidine-1-carboxylate (1.36 g, 2.69 mmol) and tin (II) chloride dihydrate (6.48 g, 28.7 mmol) were combined in ethyl acetate (20 mL) and heated at reflux for 4 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate (2×), brine (2×), dried over sodium sulfate and concentrated. The crude product was dissolved in tetrahydrofuran (10 mL), cooled to 0° C. and treated with di-tert-butyl carbonate (0.59 g, 2.69 mmol) and 10 N sodium hydroxide (0.65 mL). The reaction was allowed to warm to room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water (2×), brine (2×), dried over sodium sulfate and concentrated. Column chromatography on silica gel (30% ethyl acetate/hexanes) gave 0.25 g (19%). LC/MS (HPLC method 3): tR=2.99 min, 477.05 (MH)+.

Workup

  1. temperatureheated
  2. temperatureat reflux for 4 h
  3. washwashed with saturated sodium bicarbonate (2×), brine (2×)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in tetrahydrofuran (10 mL)
  7. temperaturecooled to 0° C.
  8. temperatureto warm to room temperature overnight
  9. washwashed with water (2×), brine (2×)
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated
  12. customColumn chromatography on silica gel (30% ethyl acetate/hexanes) gave 0.25 g (19%)

Sources & evidence

ORD record
ord-c06f1bcd06fb4263b65757627fc87c89
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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