Morpholine → Ethyl 2-(4-morpholinylmethyl)-1,3-thiazole-4-carboxylate

HRID 244653Notes

Reaction equation

HRID 244653 reaction equation
[CH:1]([C:3]1[S:4][CH:5]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:7]=1)=O.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO>[N:13]1([CH2:1][C:3]2[S:4][CH:5]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:7]=2)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 11355896Ethyl 2-formyl-1,3-thiazole-4-carboxylate

Product 1

HCID 13121935Ethyl 2-(4-morpholinylmethyl)-1,3-thiazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of ethyl 2-formyl-1,3-thiazole-4-carboxylate (315 mg) in anhydrous DCM (25 ml) was added morpholine (0.164 ml) and the mixture stirred under nitrogen for 3 h at RT. Sodium triacetoxyborohydride (759 mg) was added and the mixture stirred at RT for 16 h. Sodium bicarbonate (50 ml) and DCM (50 ml) were added and the aqueous layer was extracted with DCM (2×25 ml) using a hydrophobic frit. The solvent was removed in vacuo, the residue was dissolved in DCM (5 ml) and purified by chromatography on silica gel eluting with a gradient of 0-100% ethyl acetate in cyclohexane over 30 min. The solvent was removed in vacuo to give a white solid. The solid was dissolved in methanol (15 ml) and loaded onto an SCX SPE cartridge (50 g), which was preconditioned with methanol and allowed to stand for 15 min. The column was washed with methanol (50 ml) and elution with 2M ammonia in ethanol gave the title compound.

Workup

  1. stirringthe mixture stirred at RT for 16 h
  2. extractionthe aqueous layer was extracted with DCM (2×25 ml)
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in DCM (5 ml)
  5. custompurified by chromatography on silica gel eluting with a gradient of 0-100% ethyl acetate in cyclohexane over 30 min
  6. customThe solvent was removed in vacuo
  7. customto give a white solid
  8. waitto stand for 15 min
  9. washThe column was washed with methanol (50 ml) and elution with 2M ammonia in ethanol

Sources & evidence

ORD record
ord-3efd34b6c7f24a02a78824e24860d324
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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