Morpholine → HCID 66748298, compound

HRID 2402075Notes

Reaction equation

HRID 2402075 reaction equation
Br[C:2]1[S:3][C:4]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[N:6]=1.C(=O)([O-])[O-].[K+].[K+].[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>CN1CCCC1=O>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:7][C:5]2[N:6]=[C:2]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[S:3][C:4]=2[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 66747997HCID 66747997, compound

Product 1

HCID 66748298HCID 66748298, compoundYield 80.8%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of ethyl 2-bromo-4-(4-chlorobenzyl)thiazole-5-carboxylate (4.19 g, 11.6 mmol, prepared as described in Example 10) in N-methylpyrrolidinone (12.2 mL) was added potassium carbonate (3.21 g, 23.2 mmol) and morpholine (1.52 mL, 17.4 mmol) and the resulting mixture was heated to 130 degrees for 90 minutes. The reaction was cooled and the volatiles were removed by concentration at 65 degrees under oil pump vacuum. The residue was taken up in DCM (100 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted with DCM (50 mL). The combined DCM layers were dried over MgSO4, filtered, and concentrated to give the crude product, which was purified by silica gel chromatography (ethyl acetate/hexane=0/100→35/65) to give 3.44 g of the title compound as a white solid. (80% yield). LC/MS (FA) ES+ 367. 1H NMR (300 MHz, CDCl3) δ: 7.32-7.27 (m, 2H), 7.24-7.20 (m, 2H), 4.28 (s, 2H), 4.27 (q, 2H, J=7.2 Hz), 3.80-3.76 (m, 4H), 3.53-3.48 (m, 4H), 1.32 (t, 3H, J=7.2 Hz).

Workup

  1. temperaturethe resulting mixture was heated to 130 degrees for 90 minutes
  2. temperatureThe reaction was cooled
  3. customthe volatiles were removed by concentration at 65 degrees under oil pump vacuum
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with DCM (50 mL)
  6. dry with materialThe combined DCM layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product, which
  10. customwas purified by silica gel chromatography (ethyl acetate/hexane=0/100→35/65)

Sources & evidence

ORD record
ord-52f37496a9344466805902c9c5ef7e8e
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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