1-Propanol → Methyl 4-(2-chloro-5-methylpyrimidin-4-yl)-2-methoxybenzoate

HRID 449803Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH3:9])=[CH:4][N:3]=1.[CH3:10][O:11][C:12]1[CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=[CH:18][C:13]=1[C:14]([O:16][CH3:17])=[O:15].C(O)CC.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:20]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([O:11][CH3:10])[CH:21]=2)[C:5]([CH3:9])=[CH:4][N:3]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 2,4-dichloro-5-methylpyrimidine (244 mg, 1.5 mmol) and methyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (210 mg, 1.0 mmol) in toluene (3 mL) were added n-propanol (1 mL), aqueous sodium bicarbonate (2 M, 1.5 μL) and tetrakis(triphenylphosphine)palladium[0] (116 mg, 0.1 mmol). The reaction was heated at 110° C. for 40 h, then partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous layer was extracted twice further with ethyl acetate and the combined organic fractions were washed with water, brine then dried (sodium sulfate), filtered and concentrated. Silica gel chromatography using 30-60% ethyl acetate/petroleum spirit as eluent provided methyl 4-(2-chloro-5-methylpyrimidin-4-yl)-2-methoxybenzoate as a cream solid (165 mg, 56%); LC-ESI-MS (method B): rt 6.2 min.; m/z 293.3/295.3 [M+H]+.

Workup

custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
extractionThe aqueous layer was extracted twice further with ethyl acetate
washthe combined organic fractions were washed with water, brine
dry with materialthen dried (sodium sulfate)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-2e114b481fcb4ba58870680cfa99b50d
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486941B2

Reaction notes

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