Sodium hydride → 4-[1-(5-Bromo-pyridin-3-yl)-ethyl]-morpholin-3-one
Reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][C:2]1=[O:7].[H-].[Na+].[Br:10][C:11]1[CH:12]=[N:13][CH:14]=[C:15]([CH:17](Br)[CH3:18])[CH:16]=1.[NH4+].[Cl-]>CN(C=O)C.O.CCOC(C)=O>[Br:10][C:11]1[CH:16]=[C:15]([CH:17]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][C:2]2=[O:7])[CH3:18])[CH:14]=[N:13][CH:12]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Procedure
Morpholin-3-one (650 mg, 6.4 mmol) is dissolved in DMF (20 mL) and 60% sodium hydride in mineral oil (190 mg, 4.8 mmol) is added at 0° C. The mixture is stirred for 15 min and 3-bromo-5-(1-bromo-ethyl)-pyridine (850 mg, 3.2 mmol) is added at 0° C. The mixture is warmed up to room temperature for 2 hrs. Then saturated NH4Cl aqueous solution (25 mL) is added along with EtOAc (50 mL) and water (50 mL). The mixture is stirred for 10 min and the aqueous layer is separated and extracted with EtOAc (2×50 mL). The organic layers are combined, washed with water (3×30 mL) and concentrated to give the crude product. Purification by flash column chromatography affords 750 mg of 4-[1-(5-bromo-pyridin-3-yl)-ethyl]-morpholin-3-one. 4-[1-(5-Bromo-pyridin-3-yl)-ethyl]-morpholin-3-one (750 mg, 2.6 mmol) is coupled with Intermediate H (3.1 mmol, using crude) to give 850 mg of the titled product using Suzuki Coupling Method VI.
Workup
- stirringThe mixture is stirred for 10 min
- customthe aqueous layer is separated
- extractionextracted with EtOAc (2×50 mL)
- washwashed with water (3×30 mL)
- concentrationconcentrated
- customto give the crude product
- customPurification by flash column chromatography
Sources & evidence
- ORD record
- ord-878d7b82ef7845979267f7ab26d5e0ef
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09181272B2
Reaction notes
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