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

HRID 532826Notes

Reaction equation

HRID 532826 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, 41-1, 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-8219d29ea1464a0daea3e2e7636d7c7b
Source dataset
uspto-grants-2014_10
Patent number
US08853202B2

Reaction notes

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