2-(Di-tert-butylphosphino)biphenyl → 4-((1R)-1-phenylethyl)-(2S)-2-(4-(N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)morpholine
Reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@@H:13]1[CH2:17][CH2:16][O:15][CH2:14]1.Br[C:19]1[CH:24]=[CH:23][C:22]([C@@H:25]2[O:30][CH2:29][CH2:28][N:27]([C@@H:31]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH3:32])[CH2:26]2)=[CH:21][CH:20]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>C(O)(C)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:33]1([C@H:31]([N:27]2[CH2:28][CH2:29][O:30][C@@H:25]([C:22]3[CH:23]=[CH:24][C:19]([NH:12][C@@H:13]4[CH2:17][CH2:16][O:15][CH2:14]4)=[CH:20][CH:21]=3)[CH2:26]2)[CH3:32])[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 90 °C
Procedure
(R)-(+)-3-Aminotetrahydrofuran toluene-4-sulfonate (2.0 g, 7.7 mmol) was added to a suspension of (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (2.4 g, 6.9 mmol), palladium acetate (65 mg, 0.29 mmol), 2-(di-t-butylphosphino)biphenyl (170 mg, 0.57 mmol), and sodium tert-butoxide (3.4 g, 35.4 mmol) in tert-butanol (50 ml) at room temperature. After heating at 90° C. for 6 hours, the resulting suspension was passed through a Celite column. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography eluting 5-10% methanol in chloroform to afford 4-((1R)-1-phenylethyl)-(2S)-2-(4-(N-((3R)-tetrahydrofuran-3-yl)amino)phenyl)morpholine (1.3 g, 53%) as white crystals.
Workup
- concentrationThe filtrate was concentrated under reduced pressure
- customthe residue was purified by silica gel chromatography
- washeluting 5-10% methanol in chloroform
Sources & evidence
- ORD record
- ord-78712ee937bd4d94b82eec3d1cabcf62
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08106045B2
Reaction notes
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