Binap, (A+-)- → [(R)-1-(4-Chloro-3-methyl-phenyl)-propyl]-(4-[1,3]dioxolan-2-yl-5-fluoro-pyridin-2-yl)-amine

HRID 1629739Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[C:5]([F:13])=[CH:4][N:3]=1.Cl.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C@H:22]([NH2:25])[CH2:23][CH3:24])=[CH:18][C:17]=1[CH3:26].CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C@H:22]([NH:25][C:2]2[CH:7]=[C:6]([CH:8]3[O:12][CH2:11][CH2:10][O:9]3)[C:5]([F:13])=[CH:4][N:3]=2)[CH2:23][CH3:24])=[CH:18][C:17]=1[CH3:26]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of INT 44 (370 mg, 1.492 mmol), (R)-1-(4-chloro-3-methyl-phenyl)-propylamine hydrochloride (394 mg, 1.790 mmol) and sodium tert-butoxide (344 mg, 3.58 mmol) in degassed toluene (5.8 mL) was added Pd2(dba)3 (68.3 mg, 0.075 mmol) and BINAP (93 mg, 0.149 mmol) and the resulting mixture was stirred at 80° C. for 5 hours. The mixture was diluted in EtOAc, washed with saturated aqueous sodium bicarbonate, water and brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc) to give INT 46.

Workup

washwashed with saturated aqueous sodium bicarbonate, water and brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc)
customto give INT 46

Sources & evidence

ORD record: ord-733d0fab43044471a52be03fcc9d6444
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791100B2

Reaction notes

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