Ethyl chloroformate → 6-Chloro-4-(2-chloro-phenyl)-nicotinic acid ethyl ester

HRID 1835330Notes

Reaction equation

Br[C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.C([Li])CCC.BrBr.[Li].Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26]>O1CCCC1>[CH2:28]([O:27][C:25](=[O:26])[C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[Cl:15])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1)[CH3:29]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2.00 g (6.60 mmol) 5-bromo-2-chloro-4-(2-chloro-phenyl)-pyridine in 66 ml tetrahydrofuran 4.3 ml of a solution of n-butyllithium in hexanes (1.6 M, 6.9 mmol) were added dropwise at −100° C. under argon. Thin layer chromatography showed complete bromine-lithium exchange after 5 min. After addition of 0.71 ml (7.3 mmol) ethyl chloroformate the reaction mixture was allowed to slowly warm to −78° C. and stirred at that temperature for 1 h. The reaction mixture was allowed to warm to room temperature over night. Quenching with a small amount of water was followed by dilution with tert-butyl methyl ether and washing with water and brine. The organic layer was dried with sodium sulfate and concentrated. Column chromatography afforded 1.66 g (85%) of the title compound as a light yellow solid.

Workup

customafter 5 min
temperatureto warm to room temperature over night
customQuenching with a small amount of water
washwashing with water and brine
dry with materialThe organic layer was dried with sodium sulfate
concentrationconcentrated

Sources & evidence

ORD record: ord-f9ce7f2508f84c62827669a9f278a1a2
Source dataset: uspto-grants-2004_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06770637B2

Reaction notes

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