Ethyl Acetate → 4-(3-Chloro-5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1993638Notes

Reaction equation

Cl[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C=O)C.O>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([C:2]2[C:7]([Cl:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

Conditions

Temperature: 80 °C

Procedure

Place 2,3-dichloro-5-nitro-pyridine (2.0 g, 10.36 mmol), piperazine-1-carboxylic acid tert-butyl ester (2.12 g, 11.40 mmol), and potassium carbonate (1.72 g, 12.43 mmol) in DMF (20 mL). Heat to 80° C. for 2.5 days. Cool to room temperature and add ethyl acetate and water. Separate organic layer and wash with water and saturated aq. sodium chloride. Collect organic layer, dry over Mg2SO4, filter, and concentrate under reduced pressure. Subject residue to silica gel chromatography eluting with 20% EtOAc:hexane to yield 3.29 g (93%) of 4-(3-chloro-5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester. MS(ES): m/z=341 [M+H].

Workup

temperatureCool to room temperature
washSeparate organic layer and wash with water and saturated aq. sodium chloride
dry with materialCollect organic layer, dry over Mg2SO4
filtrationfilter
concentrationconcentrate under reduced pressure
washSubject residue to silica gel chromatography eluting with 20% EtOAc

Sources & evidence

ORD record: ord-ddb6dec00f7f4fdab871ea617e4a4de5
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652015B2

Reaction notes

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