Hydrochloric Acid → HCID 86665699, compound

HRID 81077Notes

Reaction equation

HRID 81077 reaction equation
[C:1]([C:3]1[C:8](=O)[NH:7][C:6]([C:10]2[CH:21]=[CH:20][C:13]([C:14]([O:16]C(C)C)=[O:15])=[CH:12][CH:11]=2)=[CH:5][C:4]=1[S:22][CH3:23])#[N:2].P(Cl)(Cl)([Cl:26])=O.CN(C=O)C.Cl>O>[Cl:26][C:8]1[N:7]=[C:6]([C:10]2[CH:21]=[CH:20][C:13]([C:14]([OH:16])=[O:15])=[CH:12][CH:11]=2)[CH:5]=[C:4]([S:22][CH3:23])[C:3]=1[C:1]#[N:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 66927077Isopropyl 4-(5-cyano-4-(methylthio)-6-oxo-1,6-dihydropyridin-2-yl)benzoate

Product 1

HCID 86665699HCID 86665699, compoundYield 97.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
110 °C

Procedure

A suspension of isopropyl 4-(5-cyano-4-(methylthio)-6-oxo-1,6-dihydropyridin-2-yl)benzoate (1.6 g, 4.87 mmol) in phosphoryl trichloride (14.94 g, 97 mmol) was heated to 110° C. for 60 h, cooled to room temperature and carefully added to cold water (50 mL). The resultant mixture was carefully quenched with saturated. NaHCO3(200 mL), and extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed with brine (100 mL), dried (MgSO4) and concentrated to give a mixture of acid and ester. The material was treated with DMF (10 ml) and 6 N HCl (10 ml), heated to 100° C. for 1 h, cooled to room temperature and diluted with water (50 ml) and filtered. The solid was washed with water (10 ml), dried under vacuum to give 4-(6-chloro-5-cyano-4-(methylthio)pyridin-2-yl)benzoic acid (1.45 g. 70% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.31 (2H, d, J=8.53 Hz), 8.10 (2H, d, J=8.53 Hz), 7.95 (1H, s), 2.87 (3H, s); MS (ES+) m/z: 305 (M+H); LC retention time: 3.45 min (analytical HPLC Method A).

Workup

  1. temperaturecooled to room temperature
  2. customThe resultant mixture was carefully quenched with saturated
  3. extractionNaHCO3(200 mL), and extracted with ethyl acetate (3×200 mL)
  4. washThe combined organic extracts were washed with brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customto give
  8. temperatureheated to 100° C. for 1 h
  9. temperaturecooled to room temperature
  10. filtrationfiltered
  11. washThe solid was washed with water (10 ml)
  12. customdried under vacuum

Sources & evidence

ORD record
ord-59c468cc8f8142889f73897c28f150c9
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

Loading…