Morpholine → 2-(Morpholin-4-yl)-1,3-thiazole-4-carbaldehyde

HRID 2063552Notes

Reaction equation

HRID 2063552 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([CH:7]=[O:8])[N:6]=1.[NH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.CCOC(C)=O.CCCCCC.CCOC(C)=O>O1CCOCC1>[O:12]1[CH2:13][CH2:14][N:9]([C:2]2[S:3][CH:4]=[C:5]([CH:7]=[O:8])[N:6]=2)[CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8857Ethyl AcetateHCID 177504332-Bromo-1,3-thiazole-4-carboxaldehydeHCID 21226206Ethyl acetate hexane

Product 1

HCID 150535792-(Morpholin-4-yl)-1,3-thiazole-4-carbaldehydeYield 75.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a slurry of 2-bromothiazole-4-carbaldehyde (1.0 g, 5.21 mmol) in p-dioxane (5 mL) was added morpholine (1.36 g, 15.61 mmol) over 1 min. The mixture was heated to 100° C. for 1 h (monitored by TLC, EtOAc/hexane 1:1) and cooled to room temperature. EtOAc (20 mL) was added and the solid residue filtered off and washed with EtOAc (30 mL). The combined organic layer was washed with brine (30 mL) and concentrated. The residue was purified by silica gel flash column chromatography using 20 to 75% EtOAc in hexane to afford the title compound as a light tan solid (780 mg, 75%): 1H NMR (400 MHz, CDCl3) δ 9.70 (s, 1H), 7.49 (s, 1H), 3.82 (t, 4H, J=4.8 Hz), 3.56 (t, 4H, J=4.8 Hz). MS (ES) m/z 199.1 (M+H+).

Workup

  1. filtrationthe solid residue filtered off
  2. washwashed with EtOAc (30 mL)
  3. washThe combined organic layer was washed with brine (30 mL)
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-25b6c4e36387478ea3203315bab90949
Source dataset
uspto-grants-2012_10
Patent number
US08288373B2

Reaction notes

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