Cesium carbonate → (4-((5-(4-hydroxyphenyl)-1H-pyrazol-1-yl)methyl)phenyl)(pyrrolidin-1-yl)methanone

HRID 1399810Notes

Reaction equation

HRID 1399810 reaction equation
Br[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])=[CH:10][CH:9]=2)[N:5]=[CH:4][CH:3]=1.[OH:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:21][C:22]1[CH:27]=[CH:26][C:25]([C:2]2[N:6]([CH2:7][C:8]3[CH:13]=[CH:12][C:11]([C:14]([N:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)=[O:15])=[CH:10][CH:9]=3)[N:5]=[CH:4][CH:3]=2)=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343604-Hydroxyphenylboronic acidHCID 86729227(4-((5-bromo-1H-pyrazol-1-yl)methyl)phenyl)(pyrrolidin-1-yl)methanone

Product 1

HCID 136341374(4-((5-(4-hydroxyphenyl)-1H-pyrazol-1-yl)methyl)phenyl)(pyrrolidin-1-yl)methanoneYield 71.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
140 °C

Procedure

To a solution of (4-((5-bromo-1H-pyrazol-1-yl)methyl)phenyl)(pyrrolidin-1-yl)methanone (231 mg, 0.7 mmol) in dioxane:water (5:1, 25 ml) was added (4-hydroxyphenyl)boronic acid (207 mg, 1.5 mmol), Cs2CO3 (487 mg, 1.5 mmol) and Pd(dppf)Cl2 (86 mg) and the mixture purged with nitrogen. The mixture was then stirred at 140° C. under microwave mediated heating irradiation for 40 min. The mixture was diluted with water, extracted with ethyl acetate three times and the organic layer dried over Na2SO4 before concentration. The crude product was then purified by column chromatography to yield the desired product (173 mg, yield 70%). LCMS (m/z): 348.2 [M+H]+

Workup

  1. customthe mixture purged with nitrogen
  2. temperaturemediated heating
  3. customirradiation for 40 min
  4. additionThe mixture was diluted with water
  5. extractionextracted with ethyl acetate three times
  6. dry with materialthe organic layer dried over Na2SO4 before concentration
  7. customThe crude product was then purified by column chromatography

Sources & evidence

ORD record
ord-6aebc4b4fb1c4d0780f3301a3a41f95c
Source dataset
uspto-grants-2014_12
Patent number
US08906900B2

Reaction notes

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