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

HRID 921627Notes

Reaction equation

HRID 921627 reaction equation
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]

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

(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) piperdine (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 room temperature, 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 (3.27 g) as a yellow solid.

Workup

  1. customThe flask was evacuated
  2. custompurged with nitrogen (4×)
  3. custom2 d
  4. temperatureAfter cooling to room temperature
  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)

Sources & evidence

ORD record
ord-10c7322fd23d41738aec701c587eb8b7
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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