Benzophenone imine → (R)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5-methyl-morpholin-3-one
Reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C@@:8]2([CH3:15])[NH:13][C:12](=[O:14])[CH2:11][O:10][CH2:9]2)[CH:7]=1.[C:17](=[NH:30])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC(C1C=C(C(C)C)C(C2C(P(C(C)(C)C)C(C)(C)C)=CC=CC=2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:17](=[N:30][C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C@@:8]2([CH3:15])[NH:13][C:12](=[O:14])[CH2:11][O:10][CH2:9]2)[CH:7]=1)([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 105 °C
Procedure
Under a nitrogen atmosphere a solution of (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholin-3-one (building block B) (1.2 g, 4.17 mmol) in toluene (20 ml) was treated with benzophenonimine (1.59 g, 8.33 mmol), tris(dibenzylideneacetone)-dipalladium chloroform complex (133 mg, 0.125 mmol), tert-butyl X-phos (182 mg, 0.417 mmol) and sodium tert-butoxide (1.24 g, 12.5 mmol). The mixture was stirred in a sealed tube at 105° C. for 18 hours. For the workup, the brown reaction mixture was evaporated and the residue directly purified by flash chromatography on a silica-amine phase using a gradient of heptane/ethyl acetate=100:0 to 40:60 as the eluent. The (R)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5-methyl-morpholin-3-one was obtained as a yellow solid (1.53 g, 95%); (calculated) C24H21FN2O2 [388.45]; (found) [M+H]+=389.
Workup
- customFor the workup, the brown reaction mixture was evaporated
- customthe residue directly purified by flash chromatography on a silica-amine phase
Sources & evidence
- ORD record
- ord-9b70b339fbb3461ca24638931cfe8233
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09242943B2
Reaction notes
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