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

HRID 1629745Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:11](C)=[CH:10][N:9]=[C:8](Cl)[CH:7]=1)=[O:5])C.[ClH:14].[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].[CH3:27]C(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:14][C:11]1[C:6]([CH:4]([O:3][CH3:1])[O:5][CH3:27])=[CH:7][C:8]([NH:25][C@@H:22]([C:19]2[CH:20]=[CH:21][C:16]([Cl:15])=[C:17]([CH3:26])[CH:18]=2)[CH2:23][CH3:24])=[N:9][CH:10]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 2-chloro-5-methylpyridine-4-carboxylic acid ethyl ester (750 mg, 3.76 mmol), (R)-1-(4-chloro-3-methyl-phenyl)-propylamine hydrochloride (992 mg, 4.51 mmol) and sodium tert-butoxide (867 mg, 9.02 mmol) in degassed toluene (54 mL) was added Pd2(dba)3 (172 mg, 0.188 mmol) and BINAP (234 mg, 0.378 mmol) and the resulting mixture was stirred at 50° C. for 5 hours. The mixture was diluted with 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 54.

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 54

Sources & evidence

ORD record: ord-7b0497ee29e8451f99a9e00794603958
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791100B2

Reaction notes

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