Morpholine → Methyl 2-morpholinothiazole-4-carboxylate

HRID 625097Notes

Reaction equation

HRID 625097 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1.[NH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1>C1COCC1.C(OCC)(=O)C>[O:14]1[CH2:15][CH2:16][N:11]([C:2]2[S:3][CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=2)[CH2:12][CH2:13]1

Participants

5

Reactant 2

HCID 8083MorpholineHCID 2763213Methyl 2-bromothiazole-4-carboxylate

Product 1

HCID 86700889Methyl 2-morpholinothiazole-4-carboxylateYield 93.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 2-bromothiazole-4-carboxylate (0.20 g, 0.901 mmol) in THF (10 mL) was treated with morpholine (0.17 mL, 1.94 mmol) and refluxed for 18 h. The reaction was then diluted with ethyl acetate and washed with sat. NaHCO3 (1×), brine (1×) and dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (2.5×10 cm, 50% AcOEt/CH2Cl2) to give the title material (0.192 g, 92%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.44 (s, 1H) 3.82 (s, 3H) 3.75 (m, 4H) 3.45 (m, 4H).

Workup

  1. temperaturerefluxed for 18 h
  2. washwashed with sat. NaHCO3 (1×), brine (1×)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (2.5×10 cm, 50% AcOEt/CH2Cl2)

Sources & evidence

ORD record
ord-bd1ac56b2fec42e8befb10a94f938b11
Source dataset
uspto-grants-2016_04
Patent number
US09303065B2

Reaction notes

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