Sodium Carbonate → 2-Chloro-4-(thiophen-3-yl)pyrimidine

HRID 852903Notes

Reaction equation

[S:1]1[CH:5]=[CH:4][C:3](B(O)O)=[CH:2]1.[Cl:9][C:10]1[N:15]=[C:14](Cl)[CH:13]=[CH:12][N:11]=1.C([O-])([O-])=O.[Na+].[Na+]>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:9][C:10]1[N:15]=[C:14]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)[CH:13]=[CH:12][N:11]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 3-thiopheneboronic acid (500 mg, 3.91 mmol) and 2,4-dichloropyrimidine (1.16 g, 7.81 mmol) in acetonitrile (20 mL) was added a 0.4 M solution of Na2CO3 (20 mL) followed by Pd(PPh3)4 (450 mg, 0.39 mmol). The suspension was degassed and heated at 90° C. for 16 h under nitrogen, cooled down, concentrated and extracted with EtOAc. Organic layer was successively washed with saturated solution of NH4Cl, brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc/CH2Cl2: 2/98) to afford the title compound 14 (680 mg, 3.46 mmol, 88% yield). 1H NMR: (400 MHz, CDCl3) δ (ppm): 8.56 (d, J=5.2 Hz, 1H), 8.19 (dd, J=3.2, 1.2 Hz, 1H), 7.66 (dd, J=5.2, 1.2 Hz, 1H), 7.46 (d, J=5.2 Hz, 1H), 7.43 (dd, J=5.2, 2.8 Hz, 1H).

Workup

customThe suspension was degassed
temperaturecooled down
concentrationconcentrated
extractionextracted with EtOAc
washOrganic layer was successively washed with saturated solution of NH4Cl, brine
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography on silica gel (EtOAc/CH2Cl2: 2/98)

Sources & evidence

ORD record: ord-b49070a6df3e441fa065774ef040255d
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07253204B2

Reaction notes

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