Hydrochloric Acid → tert-Butyl 4-(5-nitropyridine-2-ylamino)piperidine-1-carboxylate

HRID 511140Notes

Reaction equation

HRID 511140 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][N:17]=1.C(N(CC)CC)C.Cl>O1CCCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 783082-Chloro-5-nitropyridineHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 53255493tert-Butyl 4-(5-nitropyridine-2-ylamino)piperidine-1-carboxylateYield 82.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-amino-piperidine-1-carboxylic acid tert-butyl ester (440 mg; 2.2 mmol), 2-chloro-5-nitro-pyridine (316 mg; 2.0 mmol), and triethylamine (420 μL; 3.0 mL) is dissolved in tetrahydrofuran (6 mL) and the resulting mixture is irradiated in a mono-mode microwave oven for 6 hours at 120° C. The reaction mixture is then treated by water (10 mL) and the pH of the aqueous phase is set to 4-5 by the addition of aqueous 1N hydrochloric acid. The aqueous phase is then extracted with dichloromethane (2×20 mL), the combined organic layers are washed with brine (10 mL), dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude residue is then purified by column chromatography on silica gel (dichloromethane:ethyl acetate 1:0 and then 5:1) to afford the desired product (533 mg; 1.65 mmol).

Workup

  1. customthe resulting mixture is irradiated in a mono-mode microwave oven for 6 hours at 120° C
  2. extractionThe aqueous phase is then extracted with dichloromethane (2×20 mL)
  3. washthe combined organic layers are washed with brine (10 mL)
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue is then purified by column chromatography on silica gel (dichloromethane:ethyl acetate 1:0

Sources & evidence

ORD record
ord-b23f2a122ec14349846ca3c2c77b3039
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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