Nicotinic Acid → 2-Chloronicotinic acid

HRID 901225Notes

Reaction equation

HRID 901225 reaction equation
C([O:3][C:4]([C:6]1[C:7](=O)[NH:8][C:9]2[C:14]([C:15]=1Cl)=CN=CC=2)=[O:5])C.[Cl:18]C1C=CN=CC=1.C(O)(=O)C1C=CC=NC=1.[Li+].CC([N-]C(C)C)C>>[Cl:18][C:7]1[N:8]=[CH:9][CH:14]=[CH:15][C:6]=1[C:4]([OH:3])=[O:5]

Participants

5

Reactant 4

HCID 938Nicotinic AcidHCID 122884-Chloropyridine2×HCID 2724682Lithium diisopropylamideHCID 59699624HCID 59699624, compound

Product 1

HCID 762582-Chloronicotinic acid

Procedure

Alternatively, the intermediate 4-chloro-2-oxo-1,2-dihydro-[1,6]-naphthyridine-3-carboxylic acid ethyl ester, depicted by formula 37 in Scheme 15 can be prepared from 4-chloro pyridine or nicotinic acid as shown in Scheme 16. Ortholithiation of 4-chloropyridine by LDA followed by quenching with dry ice or lithiation of nicotinic acid followed by quenching with hexachloroethane can give chloronicotinic acid intermediate, depicted by formula 39 in Scheme 16. Amination of this intermediate can give 3-(4-methoxy-benzylamino)-nicotinic acid, depicted by formula 40 in Scheme 16, which was converted to 1-(4-methoxy-benzyl)-1H-pyrido[4,3-d][1,3]oxazine-2,4-dione depicted by formula 41 in Scheme 16, by treating with trichloromethyl chloroformate. This intermediate can be converted into 4-chloro-2-oxo-1,2-dihydro-[1,6]-naphthyridine-3-carboxylic acid ethyl ester, depicted by formula 37 in Scheme 15, as shown in Scheme 16.

Workup

  1. customby quenching with dry ice or lithiation of nicotinic acid
  2. customby quenching with hexachloroethane

Sources & evidence

ORD record
ord-ce7dfda19c4142619a38b8a9cb36911f
Source dataset
uspto-grants-2008_04
Patent number
US07361760B2

Reaction notes

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