Hydrochloric Acid → Methyl 2-chloronicotinate
Reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(Cl)(Cl)=O.[CH3:15]O.Cl>C(Cl)Cl>[CH3:15][O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][CH:9]=[N:10][C:2]=1[Cl:1]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 40 °C
Procedure
52 was prepared according to the method of Synth. Comm. 26(12), 2257-2272 (1996). To a nitrogen purged flask was charged 2-chloro-nicotinic acid (1000.0 g, 6.0 moles, 1.0 eq) followed by 9 L methylene chloride. To this was added thionyl chloride (1.4 L, 19.7 moles, 3.2 eq.) and the reaction was heated to 40° C. with vigorous stirring under nitrogen overnight. The acid chloride solution was cooled in an ice bath and methanol (3 L, 74 moles, 12 eq.) was slowly added while keeping the temperature at 20° C. The rate limiting parameter is the vigorous evolution of copious quantities of HCl gas. After the addition, HPLC analysis [Tret starting material=7.5 min, Tret 52=11 min] showed the product had formed immediately. The volatiles were removed in vacuo and the residue extracted from 10% Na2CO3 with EtOAc. The combined organics were dried (MgSO4), filtered, and concentrated to a pale yellow oil.
Workup
- custom52 was prepared
- customat 20° C
- additionAfter the addition, HPLC analysis [Tret starting material=7.5 min, Tret 52=11 min]
- customhad formed immediately
- customThe volatiles were removed in vacuo
- extractionthe residue extracted from 10% Na2CO3 with EtOAc
- dry with materialThe combined organics were dried (MgSO4)
- filtrationfiltered
- concentrationconcentrated to a pale yellow oil
Sources & evidence
- ORD record
- ord-5bf12b90b3d54104baa675ab1f4a25e4
- Source dataset
- uspto-grants-2011_10
- Patent number
- US08034950B2
Reaction notes
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