Dimethylformamide → 5-Butyl-2-chloro-nicotinic acid methyl ester

HRID 2100551Notes

Reaction equation

HRID 2100551 reaction equation
O(Cl)[Cl:2].[CH3:4][O:5][C:6](=[O:16])/[C:7](/C#N)=[CH:8]/[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].C[N:18]([CH:20]=O)[CH3:19]>>[CH3:4][O:5][C:6](=[O:16])[C:7]1[CH:8]=[C:9]([CH2:10][CH2:11][CH2:12][CH3:13])[CH:20]=[N:18][C:19]=1[Cl:2]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24646Chlorine monoxideHCID 86616607(E)-2-cyano-oct-2-enoic acid methyl ester

Product 1

HCID 866166085-Butyl-2-chloro-nicotinic acid methyl esterYield 17%

Conditions

Temperature
80 °C

Procedure

Phosporous oxychloride (4.76 ml, 51 mmol) was added within 10 minutes to an ice cold solution of (E)-2-cyano-oct-2-enoic acid methyl ester (4.65 g, 26 mmol) in DMF (12 ml) under an argon atmosphere. The reaction mixture was stirred for 14 h at 80° C. and poured onto ice water. After 3 h the mixture was extracted two times with dichloromethane, the combined extracts were washed with ice water and dried over sodium sulfate. Removal of the solvent under reduced pressure left a brown oil which was purified by column chromatography (silica gel, isopropyl acetate/heptane) to give 5-butyl-2-chloro-nicotinic acid methyl ester (1.01 g, 4.4 mmol; 17%) as yellow oil. MS: m/e=227.0 [M+H+].

Workup

  1. additionpoured onto ice water
  2. extractionAfter 3 h the mixture was extracted two times with dichloromethane
  3. washthe combined extracts were washed with ice water
  4. dry with materialdried over sodium sulfate
  5. customRemoval of the solvent under reduced pressure
  6. waitleft a brown oil which
  7. customwas purified by column chromatography (silica gel, isopropyl acetate/heptane)

Sources & evidence

ORD record
ord-a067bf2053a04d929045bebf64a1c771
Source dataset
uspto-grants-2009_08
Patent number
US07572801B2

Reaction notes

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