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

HRID 591126Notes

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-22b8c07521bc4ce7b49ff0c74518356d
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238628B2

Reaction notes

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