Water → 1-Boc-4-(6-methyl-5-nitro-2-pyridinyl)-piperazine

HRID 1993634Notes

Reaction equation

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

Participants

Conditions

Temperature: 30 °C

Procedure

Mechanically stir mixture of 6-chloro-2-methyl-3-nitro-pyridine (Asymchem, 25.00 g, 144.9 mmol), tert-butyl 1-piperazinecarboxylate (29.68 g, 159.4 mmol), and triethylamine (23.2 mL, 167 mmol) in n-BuOH (250 mL) at 50° C. under nitrogen for 4 hours, at 65° C. for 2 hours, then at room temperature overnight. Add additional tert-butyl 1-piperazinecarboxylate (1.5 g), and heat the reaction at 65° C. for 4 hours. Cool the resulting slurry to 30° C. then add hexanes (75 mL). Cool the slurry to room temperature over 1 hour, then add water (150 mL). Allow the slurry to stand for 45 min then filter. Wash the cake with water (4×100 mL) then hexanes (100 mL) and air-dry overnight to yield 4-(6-methyl-5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester as bright yellow crystals (46.30 g, 99% yield, MS(ES): m/z=267 [M+H—C4H8]).

Workup

customat room temperature
customovernight
temperatureheat
customthe reaction at 65° C. for 4 hours
temperatureCool the slurry to room temperature over 1 hour
waitto stand for 45 min
filtrationthen filter
washWash the cake with water (4×100 mL)
dry with materialhexanes (100 mL) and air-dry overnight

Sources & evidence

ORD record: ord-1b5e40437390426ea79d40404430ecaa
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652015B2

Reaction notes

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