Hydrochloric Acid → 2-(2,5-Dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid

HRID 1986225Notes

Reaction equation

HRID 1986225 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[C:7]([C:10]1[C:18]2[CH:17]=[C:16](B(O)O)[S:15][C:14]=2[CH:13]=[CH:12][CH:11]=1)([OH:9])=[O:8].[Cl:22][C:23]1[N:28]=[C:27](Cl)[CH:26]=[C:25](Cl)[N:24]=1.[ClH:31]>COCCOC.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>[Cl:22][C:23]1[N:28]=[C:27]([C:16]2[S:15][C:14]3[CH:13]=[CH:12][CH:11]=[C:10]([C:7]([OH:9])=[O:8])[C:18]=3[CH:17]=2)[C:26]([Cl:31])=[CH:25][N:24]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 773782,4,6-TrichloropyrimidineHCID 67272237(4-Carboxybenzo[b]thiophen-2-yl)boronic acid

Product 1

HCID 866253522-(2,5-Dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acidYield 38%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

An aqueous Na2CO3 solution (2 M, 500 mL) is added dropwise to a stirred solution of (4-carboxy-benzo[b]thiophen-2-yl)boronic acid (56 g, 0.25 mol) and 2,4,6-trichloro-pyrimidine (42.1 g, 0.230 mol) in ethyleneglycol dimethyl ether (620 mL) at room temperature under nitrogen atmosphere. Upon the completion of addition, PdCl2(PPh3)2 (5.31 g, 3% mol) is added in one portion, then the reaction mixture is heated at 100° C. overnight. The mixture is cooled to 10° C., then 37% HCl (150 mL) is added in portions to form a suspension. After filtration and washing with water (300 mL×3) the solid is dried under vacuum. Then the solid is suspended in 1 L of dichloromethane/ethanol (10:1) and stirred overnight. After another round of filtration and drying, the first crop of title compound (28.0 g, 38% yield) is obtained. Mother liquor is concentrated and the residue is suspended in acetone (1 mL) and stirred overnight. After filtration, the solid is re-suspended in 200 mL of dichloromethane/ethanol (ethanol) (3:1) and stirred for 2 hours. Additional 5 g of the title compound is obtained after filtration and drying. Overall yield is 44%.

Workup

  1. additionis added in one portion
  2. temperatureThe mixture is cooled to 10° C.
  3. customto form a suspension
  4. filtrationAfter filtration
  5. washwashing with water (300 mL×3) the solid
  6. customis dried under vacuum
  7. filtrationAfter another round of filtration
  8. customdrying

Sources & evidence

ORD record
ord-20339768e4d6473c866a42823023373c
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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