Cesium carbonate → Tert-butyl (3-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate

HRID 1430798ノート

反応式

HRID 1430798 の反応式
Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[Si:19]([O:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].C(=O)([O-])[O-].[Cs+].[Cs+].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.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]>[Si:19]([O:26][CH:27]1[CH2:28][CH2:29][N:30]([C:2]2[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=2)[CH2:31][CH2:32]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 114813284-((Tert-butyldimethylsilyl)oxy)piperidineHCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate2 回

生成物 1

HCID 86708480Tert-butyl (3-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate収率 43.2%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

(I13A): A round bottom flask was charged with tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (Intermediate 1) (5.39 g, 16.25 mmol), 4-((tert-butyldimethylsilyl)oxy)piperidine (3.5 g, 16.25 mmol), cesium carbonate (10.5 g, 32.5 mmol), Pd2(dba)3 (1.488 g, 1.625 mmol) and BINAP (1.012 g, 1.625 mmol) in toluene (54.2 ml). The flask was evacuated and purged with nitrogen (4×) and heated at 100° C. 2 d. After cooling to rt, the reaction mixture was diluted with ethyl acetate and vacuum filtered through a pad of Celite. The filtrate was concentrated in vacuo. The crude residue was purified by column chromatography on the Isco system (330 g, 60-95% CH2Cl2/Hex) to provide tert-butyl (3-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate (I13A) (3.27 g) as a yellow solid.

後処理

  1. customThe flask was evacuated
  2. custompurged with nitrogen (4×)
  3. custom2 d
  4. temperatureAfter cooling to rt
  5. additionthe reaction mixture was diluted with ethyl acetate and vacuum
  6. filtrationfiltered through a pad of Celite
  7. concentrationThe filtrate was concentrated in vacuo
  8. customThe crude residue was purified by column chromatography on the Isco system (330 g, 60-95% CH2Cl2/Hex)

出典と根拠

ORDレコード
ord-c32fee01c76b4344b5ef1310a057dc13
出典データセット
uspto-grants-2015_01
特許番号
US08940736B2

反応ノート

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