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

HRID 1430798노트

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HRID 1430798 반응식
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]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 114813284-((Tert-butyldimethylsilyl)oxy)piperidineHCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate2회

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
100 °C

실험 절차

(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.

후처리

  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)

출처 및 근거

ORD 기록
ord-c32fee01c76b4344b5ef1310a057dc13
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940736B2

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