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

HRID 1629745ノート

反応式

HRID 1629745 の反応式
[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-7b0497ee29e8451f99a9e00794603958
出典データセット
uspto-grants-2014_07
特許番号
US08791100B2

反応ノート

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