Carbon Dioxide → 5-tert-Butoxycarbonylamino-2-chloroisonicotinic acid

HRID 887702Notes

Reaction equation

[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:9]=[N:10][C:11]([Cl:14])=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].CN(C)CCN(C)C.C([Li])CCC.[C:29](=[O:31])=[O:30]>C(OCC)C.C1COCC1>[C:1]([O:5][C:6]([NH:7][C:8]1[C:13]([C:29]([OH:31])=[O:30])=[CH:12][C:11]([Cl:14])=[N:10][CH:9]=1)=[O:15])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: -10 °C

Procedure

A solution of (6-chloro-pyridin-3-yl)-carbamic acid tert-butyl ester (4.19 g) in diethyl ether (150 mL) was cooled to −78° C. and N,N,N′,N′-tetramethylethylendiamine (6.60 g) was added. After slow addition of n-butyl lithium solution (1.32 M in hexane, 41.6 mL) over a time period of 10 minutes, the mixture was allowed to warm up to −10° C., stirred at this temperature for 2 hours and then was re-cooled to −78° C. The mixture was poured slowly into a stirred mixture of crushed dry ice in THF and stirred for 30 minutes. The mixture was concentrated on a rotary evaporator and water was added to the residue. The aqueous layer was washed 2× with MTB-ether and acidified with 6N hydrochloric acid to pH ˜3. The formed precipitate was filtered off, washed with water, ethyl acetate and dried in vacuum to afford 2.46 g of the title compound of the formula

Workup

temperaturewas re-cooled to −78° C
stirringstirred for 30 minutes
concentrationThe mixture was concentrated on a rotary evaporator and water
additionwas added to the residue
washThe aqueous layer was washed 2× with MTB-ether
filtrationThe formed precipitate was filtered off
washwashed with water, ethyl acetate
customdried in vacuum

Sources & evidence

ORD record: ord-f1b03f64c488414f8646163c452bb873
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08247431B2

Reaction notes

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