Cesium carbonate → HCID 131734957, compound

HRID 921947Notes

Reaction equation

HRID 921947 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.[CH2:19]1[C:23]2([CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH2:22][CH2:21][N:20]1[C:29](=[O:31])[CH3:30].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]>[C:29]([N:20]1[CH2:21][CH2:22][C:23]2([CH2:28][CH2:27][N:26]([C:2]3[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]=3)[CH2:25][CH2:24]2)[CH2:19]1)(=[O:31])[CH3:30]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 21060031HCID 21060031, compoundHCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate

Product 1

HCID 131734957HCID 131734957, compoundYield 50.5%

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 (291 mg, 0.878 mmol), 1-(2,8-diazaspiro[4.5]decan-2-yl)ethanone (160 mg, 0.878 mmol), Pd2dba3 (80 mg, 0.088 mmol), BINAP (164 mg, 0.263 mmol), and Cs2CO3 (858 mg, 2.63 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) gave tert-butyl (3-(2-acetyl-2,8-diazaspiro[4.5]decan-8-yl)-2-chloro-5-cyanophenyl)carbamate (192 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-cf34651fa56b43b687960f480743c8d8
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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