Ethyl Acetate → 4-Chloro-6-thiophen-2-yl-pyrimidine

HRID 1752001Notes

Reaction equation

HRID 1752001 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[S:9]1[CH:13]=[CH:12][CH:11]=[C:10]1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C>C(COC)OC.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.CCCCCC>[Cl:1][C:2]1[CH:7]=[C:6]([C:10]2[S:9][CH:13]=[CH:12][CH:11]=2)[N:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 709434,6-DichloropyrimidineHCID 27339602-Thiopheneboronic acid

Product 1

HCID 249021114-Chloro-6-thiophen-2-yl-pyrimidineYield 62.8%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 8058HexaneSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

4,6-dichloropyrimidine (22.2 g, 149.1 mmol), thiophene-2-boronic acid (20.0 g, 156.3 mmol, 1.05 equiv), Na2CO3 (28.8 g, 271.4 mmol, 1.8 equiv) and Pd(PPh3)2Cl2 (2.9 g, 4.2 mmol, 0.03 equiv) were refluxed in dimethoxyethane-water (727:238 mL) mixed solvent system for 16 h. Reaction was monitored by TLC (using ethyl acetate:n-hexane, 1:9). Reaction mixture was cooled and the subject compound was extracted using dichloromethane. Subject compound was purified by flash chromatography (5% ethyl acetate:n-hexane) to yield 18.4 g of 3 (Yield=62.8%).

Workup

  1. additionmixed solvent system for 16 h
  2. customReaction
  3. customReaction mixture
  4. temperaturewas cooled
  5. extractionthe subject compound was extracted
  6. customSubject compound was purified by flash chromatography (5% ethyl acetate:n-hexane)

Sources & evidence

ORD record
ord-70aaa04bad8a4bd8ab9e7e1693f9b617
Source dataset
uspto-grants-2015_10
Patent number
US09162987B2

Reaction notes

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