Cesium carbonate → Tert-butyl (2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)carbamate

HRID 921942Notes

Reaction equation

HRID 921942 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.[CH3:19][N:20]1[CH2:24][CH2:23][C:22]2([CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[C:21]1=[O:30].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.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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:18][C:3]1[C:2]([N:27]2[CH2:28][CH2:29][C:22]3([C:21](=[O:30])[N:20]([CH3:19])[CH2:24][CH2:23]3)[CH2:25][CH2:26]2)=[CH:7][C:6]([C:8]#[N:9])=[CH:5][C:4]=1[NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 3270242-Methyl-2,8-diazaspiro[4.5]decan-1-oneHCID 634876Binap, (A+-)-HCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate

Product 1

HCID 130364299Tert-butyl (2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)carbamateYield 44.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (349 mg, 1.052 mmol), 2-methyl-2,8-diazaspiro[4.5]decan-1-one (177 mg, 1.052 mmol), Pd2dba3 (96 mg, 0.105 mmol), BINAP (197 mg, 0.316 mmol), and Cs2CO3 (1028 mg, 3.16 mmol) in Dioxane (15 mL) was evacuated and filled with nitrogen 3× and heated at 105° C. overnight. The reaction mixture was filtered through a plug of celite and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10% to 100% EtOAc in Hexane) to give tert-butyl (2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)carbamate (197 mg)

Workup

  1. customwas evacuated
  2. additionfilled with nitrogen 3×
  3. filtrationThe reaction mixture was filtered through a plug of celite
  4. concentrationthe filtrate was concentrated
  5. customThe crude product was purified by flash chromatography on silica gel using
  6. washan automated ISCO system (40 g column, eluting with 10% to 100% EtOAc in Hexane)

Sources & evidence

ORD record
ord-bc320ed882f843f6a354e4360b76d296
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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