Acetic Acid → HCID 18538842, compound

HRID 1394331Notes

Reaction equation

HRID 1394331 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:22]=[N+:23]=[N-:24].[Na+].N([O-])=O.[Na+].[C:30](O)(=O)C>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH:30]=[N:24][N:23]=[N:22]3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 33557Sodium AzideHCID 21876872tert-Butyl 4-(4-aminobenzyl)piperidine-1-carboxylateHCID 23668193Sodium Nitrite

Product 1

HCID 18538842HCID 18538842, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 1-tert-butoxycarbonyl-4-(4-aminobenzyl)piperidine (1 g, 3.46 mmol) in acetic acid (14 mL) were added orthoethyl formate (2.4 mL, 20.7 mmol) and sodium azide (0.27 g, 4.13 mmol), and the mixture was stirred at room temperature for 30 minutes and at 80° C. for 2 hours. The mixture was cooled to room temperature. To the mixture were added water (20 mL) and a solution of sodium nitrite (4.3 g) in water (20 mL), and the mixture was stirred at room temperature for 10 minutes and extracted with ethyl acetate. The extract was washed with aqueous solution of sodium hydrogencarbonate and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3) to give 1-tert-butoxycarbonyl-4-[4-(1H-tetrazol-1-yl)benzyl]piperidine (950 mg) as colorless powdery crystals. This compound (950 mg, 2.78 mmol) was dissolved in ethyl acetate (10 mL). To the solution was added 4N-hydrogen chloride in ethyl acetate (10 mL), and the mixture was stirred at room temperature for 2 hours. The resulting crystals were collected by filtration, washed with ethyl acetate (5 mL) and dried to give the titled compound (697 mg) as colorless powdery crystals.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with aqueous solution of sodium hydrogencarbonate and saturated sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customthe concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3)

Sources & evidence

ORD record
ord-87361b72e1ab4f019c9424c2769e730e
Source dataset
uspto-grants-2008_03
Patent number
US07348324B2

Reaction notes

Loading…