Cesium carbonate → 2,4-Difluoro-5-(pyrimidin-5-yl)benzaldehyde

HRID 1907423Notes

Reaction equation

HRID 1907423 reaction equation
[N:1]1[CH:6]=[C:5](B(O)O)[CH:4]=[N:3][CH:2]=1.Br[C:11]1[C:12]([F:20])=[CH:13][C:14]([F:19])=[C:15]([CH:18]=1)[CH:16]=[O:17].C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.CCO.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:19][C:14]1[CH:13]=[C:12]([F:20])[C:11]([C:5]2[CH:6]=[N:1][CH:2]=[N:3][CH:4]=2)=[CH:18][C:15]=1[CH:16]=[O:17]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 222607695-Bromo-2,4-difluorobenzaldehyde

Product 1

HCID 866853452,4-Difluoro-5-(pyrimidin-5-yl)benzaldehydeYield 51.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of bis(triphenylphosphine)palladium(II) chloride (0.56 g, 0.80 mmol), pyrimidin-5-ylboronic acid (0.99 g, 8.0 mmol), 5-bromo-2,4-difluorobenzaldehyde (0.88 g, 3.98 mmol), cesium carbonate (2.59 g, 7.96 mmol) in DME (13 mL), EtOH (7 mL) and water (7 mL) was heated at 100° C. for 45 min, and the crude reaction mixture was subjected to HPLC separation eluting with 0-100% A/B (A: 95% H2O/5% MeCN, 10 MM NH4OAc; B: 5% H2O/95% MeCN, 10 mM NH4OAC over 30 min period to give the title compound as a white solid (450 mg, 51% yield). 1H NMR (500 MHz, CHLOROFORM-d) δ 10.40-10.33 (m, 1H), 9.28 (s, 1H), 8.94 (d, J=1.2 Hz, 2H), 8.06 (dd, J=8.4, 7.8 Hz, 1H), 7.15 (t, J=9.9 Hz, 1H), 10.37 (s, 1H).

Workup

  1. customthe crude reaction mixture
  2. customwas subjected to HPLC separation
  3. washeluting with 0-100% A/B (A: 95% H2O/5% MeCN, 10 MM NH4OAc

Sources & evidence

ORD record
ord-2d98847a3b424bbba6a8ec374fa7b950
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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