Dichloromethane → (E)-methyl 5-(2-ethoxyvinyl)-2-(methylthio)pyrimidine-4-carboxylate

HRID 1480803Notes

Reaction equation

HRID 1480803 reaction equation
[CH2:1]([O:3]/[CH:4]=[CH:5]/B1OC(C)(C)C(C)(C)O1)[CH3:2].Br[C:16]1[C:17]([C:24]([O:26][CH3:27])=[O:25])=[N:18][C:19]([S:22][CH3:23])=[N:20][CH:21]=1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.CCOC(C)=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]>[CH2:4]([O:3]/[CH:1]=[CH:2]/[C:16]1[C:17]([C:24]([O:26][CH3:27])=[O:25])=[N:18][C:19]([S:22][CH3:23])=[N:20][CH:21]=1)[CH3:5]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 2794729Methyl 5-bromo-2-(methylsulfanyl)pyrimidine-4-carboxylateHCID 219739081-Ethoxyethene-2-boronic acid pinacol ester

Product 1

HCID 89996170(E)-methyl 5-(2-ethoxyvinyl)-2-(methylthio)pyrimidine-4-carboxylateYield 63%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Preparation 29, 4.34 g, 21.91 mmol), methyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate (Preparation 30, 3.81 g, 14.48 mmol) and Pd(dppf)Cl2.DCM (505 mg, 0.618 mmol) was dissolved in THF (45 mL) and 2M sodium carbonate in water (15 mL) and heated to 65° C. for 18 hours. The mixture was diluted with EtOAc and quenched with brine. The aqueous layer was extracted with EtOAc three times. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by silica gel column chromatography eluting with 0 to 10% EtOAc in cyclohexane to give the title compound (2.30 g, 63%).

Workup

  1. customquenched with brine
  2. extractionThe aqueous layer was extracted with EtOAc three times
  3. washThe combined organic layers were washed with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting with 0 to 10% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-7430976adfc344cebaf6eb66eb6ba3a0
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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