Cyclohexylamine → (S)-2-(4-(cyclohexylamino)phenyl)-4-((R)-1-phenylethyl)morpholine

HRID 424420Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C@@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:9]2)=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].[CH:28]1([NH2:34])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>[CH:28]1([NH:34][C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[O:13][CH2:12][CH2:11][N:10]([C@@H:14]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:15])[CH2:9]3)=[CH:4][CH:3]=2)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a suspension of (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (7.62 g, 22.0 mmol), palladium acetate (198 mg, 0.88 mmol), 2-(di-t-butylphosphino) biphenyl (525 mg, 1.76 mmol), and sodium tert-butoxide (2.96 g, 30.8 mmol) in toluene (40 ml) was added cyclohexylamine (3.78 ml, 33.0 mmol) at room temperature. After heating at 90° C. for 2.5 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 5-25% of ethyl acetate in hexane to afford (S)-2-(4-(cyclohexyl-amino)phenyl)-4-((R)-1-phenylethyl)morpholine (6.95 g, 87%) as white crystals.

Workup

concentrationThe filtrate was concentrated under reduced pressure
customthe residue was purified by silica gel chromatography
washeluting 5-25% of ethyl acetate in hexane

Sources & evidence

ORD record: ord-b563e047fb274ad89ed0ef0d3965c4c2
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106045B2

Reaction notes

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