Methanol → 2-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid methyl ester

HRID 554837Notes

Reaction equation

HRID 554837 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:16](=[O:17])[O:15][CH2:14][CH2:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[CH3:23][OH:24]>>[CH3:23][O:24][C:16]([C:10]1[S:9][C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[N:12][C:11]=1[CH2:13][CH2:14][OH:15])=[O:17]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 574214852-(4-Chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one

Product 1

HCID 674598562-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid methyl ester

Conditions

Temperature
55 °C

Procedure

Dissolve 2-(4-chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one (500 g, 1882 mmol) in MeOH (5 L) and add concentrated sulfuric acid (31 mL). Stir the solution at 55° C. for 15 h, then warm to 66° C. and continue stirring for an additional 4.5 h. Cool the solution to 45° C. and concentrate in vacuo to one half of the volume. Continue to cool the slurry to 20° C. Isolate the precipitate by filtration and wash the solid with cold MeOH. Dry the solid (420.5 g) under vacuum overnight. Concentrate the filtrate to about 600 mL, filter, and wash with cold MeOH to obtain more solid (40.7 g). Purify the crude materials by flash chromatography, using 10% EtOAc/CH2Cl2 as eluent, to give a total of (442 g, 80%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 7.88 (dt, J=8.8, 4.7 Hz, 2H), 7.43 (dt, J=8.7, 4.3 Hz, 2H), 4.05 (t, J=5.6 Hz, 2H), 3.90 (s, 3H), 3.43 (t, J=5.6 Hz, 2H), 3.32 (bs, 1H).

Workup

  1. temperaturewarm to 66° C.
  2. stirringcontinue stirring for an additional 4.5 h
  3. temperatureCool the solution to 45° C.
  4. concentrationconcentrate in vacuo to one half of the volume
  5. temperatureContinue to cool the slurry to 20° C
  6. customIsolate the precipitate
  7. filtrationby filtration
  8. washwash the solid with cold MeOH
  9. dry with materialDry the solid (420.5 g) under vacuum overnight
  10. concentrationConcentrate the filtrate to about 600 mL
  11. filtrationfilter
  12. washwash with cold MeOH

Sources & evidence

ORD record
ord-40cd28d6dff04dcd9984d4288a2425e9
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

Loading…