Ammonia → 1-(2,5-Dimethylpyridin-4-yl)piperidin-4-amine

HRID 451418Notes

Reaction equation

HRID 451418 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[CH:6][N+:5]([O-])=[C:4]([CH3:10])[CH:3]=1.C([N:18]1[CH2:23][CH2:22][CH:21]([NH2:24])[CH2:20][CH2:19]1)(OC(C)(C)C)=O.C(N(CC)C(C)C)(C)C.Cl.N>S1(CCCC1)(=O)=O.CO>[CH3:10][C:4]1[CH:3]=[C:2]([N:18]2[CH2:23][CH2:22][CH:21]([NH2:24])[CH2:20][CH2:19]2)[C:7]([CH3:8])=[CH:6][N:5]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 669896224-Chloro-2,5-dimethylpyridine 1-oxide

Product 1

HCID 673430771-(2,5-Dimethylpyridin-4-yl)piperidin-4-amineYield 40%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 31347SulfolaneSolvent

Conditions

Temperature
220 °C

Procedure

A mixture 4-chloro-2,5-dimethyl-pyridine 1-oxide (200 mg, 1.41 mmol), Boc-4-aminopiperidine (311 mg, 1.55 mmol) and N,N-diisopropyl ethyl amine (484 μL, 2.82 mmol) in sulfolane (1 mL) was heated to 160° C. for 30 minutes in a microwave oven followed by heating to 220° C. for 30 minutes. After the addition of aqueous hydrochloric acid (25% in water, 0.5 mL) the mixture was stirred for 18 h at ambient temperature. It was treated with ammonia in methanol and concentrated. Purification by chromatography (SiO2, dichloromethane/methanol/ammonia=95:4.5:0.5 to 90:9:1) afforded the title compound (99 mg, 40%) as a light brown oil.

Workup

  1. concentrationconcentrated
  2. customPurification by chromatography (SiO2, dichloromethane/methanol/ammonia=95:4.5:0.5 to 90:9:1)

Sources & evidence

ORD record
ord-c7ff11ef5998473a96c9b2c71d6bc4cb
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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