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

HRID 1629745노트

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HRID 1629745 반응식
[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

참가 물질

8

반응물 4

HCID 634876Binap, (A+-)-HCID 2763069Ethyl 2-chloro-5-methylisonicotinateHCID 23676156Sodium t-butoxideHCID 57517333(R)-1-(4-chloro-3-methyl-phenyl)-propylamine hydrochloride

생성물 1

HCID 67345901(5-Chloro-4-dimethoxymethyl-pyridin-2-yl)-[(R)-1-(4-chloro-3-methyl-phenyl)-propyl]-amine

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

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.

후처리

  1. washwashed with saturated aqueous sodium bicarbonate, water and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc)
  6. customto give INT 54

출처 및 근거

ORD 기록
ord-7b0497ee29e8451f99a9e00794603958
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791100B2

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