Hydrochloric Acid → HCID 56832760, compound

HRID 2402121Notes

Reaction equation

HRID 2402121 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][C:12]3[N:13]=[C:14]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[S:15][C:16]=3[C:17]([O:19]CC)=[O:18])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.O1CCCC1.CO.[OH-].[Li+].Cl>O>[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][C:12]3[N:13]=[C:14]([N:22]4[CH2:23][CH2:24][O:25][CH2:26][CH2:27]4)[S:15][C:16]=3[C:17]([OH:19])=[O:18])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 66749560HCID 66749560, compound

Product 1

HCID 56832760HCID 56832760, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

Ethyl 4-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-2-(morpholin-4-yl)-1,3-thiazole-5-carboxylate (58.0 mg, 0.000148 mol) was placed in a 50 ml round bottom flask equipped with a stirbar. Tetrahydrofuran (2.25 mL, 0.0277 mol) and methanol (0.50 mL, 0.012 mol) were added and the mixture was stirred to give a clear solution. A solution of lithium hydroxide in water (2.0M, 0.750 mL, 0.00150 mol) was added in a single portion, resulting in a pale yellow solution which was stirred at room temperature under an atmosphere of nitrogen for 15 minutes. The reaction was then heated at reflux for 2.5 hours, cooled to rt, and diluted with water (˜25 ml) to give a clear slightly gray solution, which was allowed to stir at room temperature overnight under an atmosphere of nitrogen. 1 N HCl (˜1.8 ml) was slowly added to the stirring solution to lower the pH to ˜3 (pH paper) whereupon a white precipitate formed. The mixture was stirred for ˜15 minutes, at which point the solid was collected on a fritted funnel, washed with water, and dried on the funnel with house vacuum under a stream of nitrogen for several hours to yield 4-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-2-(morpholin-4-yl)-1,3-thiazole-5-carboxylic acid (110) (45 mg, 84% yield) as a slightly gray powder. LC/MS (FA) ES+ 363; 1H NMR (300 MHz, DMSO) δ 12.65 (s, 1H), 6.76-6.64 (m, 3H), 4.17 (s, 4H), 4.08 (s, 2H), 3.77-3.61 (m, 4H), 3.51-3.34 (m, 4H).

Workup

  1. customequipped with a stirbar
  2. customto give a clear solution
  3. customresulting in a pale yellow solution which
  4. stirringwas stirred at room temperature under an atmosphere of nitrogen for 15 minutes
  5. temperatureThe reaction was then heated
  6. temperatureat reflux for 2.5 hours
  7. customto give a clear slightly gray solution, which
  8. stirringto stir at room temperature overnight under an atmosphere of nitrogen
  9. customformed
  10. stirringThe mixture was stirred for ˜15 minutes, at which point the solid
  11. customwas collected on a fritted funnel
  12. washwashed with water
  13. customdried on the funnel with house vacuum under a stream of nitrogen for several hours

Sources & evidence

ORD record
ord-35d671ca7a4d48109849a0dd308ee747
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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