Sodium Carbonate → 5-Bromo-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole

HRID 2402045Notes

Reaction equation

HRID 2402045 reaction equation
Br[C:2]1[S:3][C:4]([Br:15])=[C:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[N:6]=1.[N:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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]>[Br:15][C:4]1[S:3][C:2]([C:19]2[CH:20]=[CH:21][N:16]=[CH:17][CH:18]=2)=[N:6][C:5]=1[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 667475662,5-Dibromo-4-(4-chlorobenzyl)thiazole

Product 1

HCID 667479255-Bromo-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazoleYield 26%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 2,5-dibromo-4-(4-chlorobenzyl)thiazole (12.9 grams, 35.1 mmol) in DME (365 mL) was added pyridine-4-boronic acid (5.61 g, 45.6 mmol), 1M sodium carbonate (70.2 mL, 70.2 mmol), and PdCl2(dppf) (2.89 g, 3.51 mmol). The reaction was degassed with argon and stirred at 85° C. overnight. The reaction was cooled and taken up in ethyl acetate (400 mL) and saturated sodium bicarbonate (200 mL). The insolubles were filtered through celite and the bed was washed with ethyl acetate (100 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→70/30) followed by another silica gel chromatography (ethyl acetate/hexanes=0/100→100/0) to give 3.3 grams of the title compound as a brown solid (26% yield). LC/MS (FA) ES+ 365, 367. 1H NMR (300 MHz, CDCl3) δ: 8.70-8.67 (m, 2H), 7.70-7.67 (m, 2H), 7.28-7.26 (m, 4H), 4.13 (s, 2H).

Workup

  1. customThe reaction was degassed with argon
  2. temperatureThe reaction was cooled
  3. filtrationThe insolubles were filtered through celite
  4. washthe bed was washed with ethyl acetate (100 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (100 mL)
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→70/30)

Sources & evidence

ORD record
ord-1319087e08664726a3c35e22d033e4e4
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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