Butyric Acid → HCID 12263412, compound

HRID 2401857Notes

Reaction equation

HRID 2401857 reaction equation
[C:1]([OH:6])(=[O:5])[CH2:2][CH2:3][CH3:4].[CH:7](O)(C)[CH3:8].[N:11]1([C:17](=[S:19])[NH2:18])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1>>[CH3:4][C:3]1[N:18]=[C:17]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[S:19][C:2]=1[C:1]([O:6][CH2:7][CH3:8])=[O:5]

Participants

4

Reactant 3

HCID 264Butyric AcidHCID 3776IsopropanolHCID 23935444-Morpholinecarbothioamide

Product 1

HCID 12263412HCID 12263412, compoundYield 82%

Procedure

In a 100 mL round bottomed flask, to a solution of butanoic acid, 2-chloro-3-oxo-, ethyl ester (11.2 g, 68.4 mmol) in isopropyl alcohol (250 mL, 3300 mmol) was added morpholine-4-carbothioicacidamide (10.0 g, 68.4 mmol). The mixture was stirred at reflux for 1 hour, and then stirred at room temperature for 3 days. Volatiles were removed in vacuo, and the resulting residue was dissolved in ethyl acetate and diluted with saturated, aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel, the layers were separated, and the organic layer dried with Na2SO4, filtered and concentrated in vacuo. The crude product was dissolved in DCM, adsorbed onto silica gel, and purified via column chromatography (120 g Isco column, gradient elution, 0-100% EtOAc/hexanes) to afford ethyl 4-methyl-2-(morpholin-4-yl)-1,3-thiazole-5-carboxylate (14.51 g, yield for 2 steps, 82%). LC/MS: (FA) ES+ 257, 259; 1H NMR (400 MHz, CDCl3) δ 4.26 (dd, J=7.1, 7.1, 2H), 3.87-3.67 (m, 4H), 3.59-3.42 (m, 4H), 2.55 (s, 3H), 1.33 (dd, J=7.1, 7.1, 3H).

Workup

  1. temperatureat reflux for 1 hour
  2. stirringstirred at room temperature for 3 days
  3. customVolatiles were removed in vacuo
  4. dissolutionthe resulting residue was dissolved in ethyl acetate
  5. additiondiluted with saturated, aqueous sodium bicarbonate
  6. customThe mixture was transferred to a separatory funnel
  7. customthe layers were separated
  8. dry with materialthe organic layer dried with Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe crude product was dissolved in DCM
  12. custompurified via column chromatography (120 g Isco column, gradient elution, 0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e368e38aa1ff40bfa3164d9d89ec0c5a
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

Loading…