Water → HCID 19742825, compound

HRID 2254611Notes

Reaction equation

HRID 2254611 reaction equation
[H-].[Na+].[NH2:3][C:4]1[C:13]([Cl:14])=[CH:12][C:7]([C:8]([O:10]C)=[O:9])=[C:6]([OH:15])[CH:5]=1.Cl[CH2:17][C:18]1[N:19]=[C:20]([CH3:23])[S:21][CH:22]=1.O>CN(C)C=O>[NH2:3][C:4]1[C:13]([Cl:14])=[CH:12][C:7]([C:8]([OH:10])=[O:9])=[C:6]([O:15][CH2:17][C:18]2[N:19]=[C:20]([CH3:23])[S:21][CH:22]=2)[CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 7363414-(Chloromethyl)-2-methyl-1,3-thiazoleHCID 14883223Methyl 4-amino-5-chloro-2-hydroxybenzoate

Product 1

HCID 19742825HCID 19742825, compoundYield 65.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 60% sodium hydride/oil dispersion (0.5 g, 12.5 mmoles) in anhydrous dimethylformamide (20 ml) under nitrogen was treated with methyl 4-amino-5-chloro-2-hydroxybenzoate (2.02 g, 10 mmoles), stirred for 30 minutes, then treated with 4-chloromethyl-2-methylthiazole (1.85 g, 12.5 mmoles). The mixture was heated to 95°±5° C. for 1.5 hours, then cooled and added to water (150 ml). The aqueous mixture was extracted with ether (2×100 ml), and the combined ethereal solution was dried (MgSO4), concentrated in vacuo, and taken up in 95% ethanol (20 ml). Water (10 ml) and 50% sodium hydroxide (10 ml) were added, and the mixture was refluxed for one hour, cooled in on ice, and concentrated in vacuo to remove most of the ethanol. Water was added to a total volume of 100 ml, and the aqueous solution was extracted with ether (2×50 ml), cooled in an ice bath, and adjusted to pH 4 with concentrated hydrochloric acid (16 ml). A resultant precipitate was filtered, washed with water, air dried, and recrystallized from 95% ethanol to yield 1.96 g (64%) of tan crystals, mp 188°-189° C.

Workup

  1. temperatureThe mixture was heated to 95°±5° C. for 1.5 hours
  2. temperaturecooled
  3. extractionThe aqueous mixture was extracted with ether (2×100 ml)
  4. dry with materialthe combined ethereal solution was dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. additionWater (10 ml) and 50% sodium hydroxide (10 ml) were added
  7. temperaturethe mixture was refluxed for one hour
  8. temperaturecooled in on ice
  9. concentrationconcentrated in vacuo
  10. customto remove most of the ethanol
  11. additionWater was added to a total volume of 100 ml
  12. extractionthe aqueous solution was extracted with ether (2×50 ml)
  13. temperaturecooled in an ice bath
  14. filtrationA resultant precipitate was filtered
  15. washwashed with water, air
  16. customdried
  17. customrecrystallized from 95% ethanol

Sources & evidence

ORD record
ord-c7a3d039a8774176a9fee7967888e58c
Source dataset
uspto-grants-1993_08
Patent number
US05236931

Reaction notes

Loading…