Water → Methyl 2-(4-fluoro-3-(1-methyl-1H-pyrazol-4-yl)phenyl)acetate

HRID 909916Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].O.[CH3:8][N:9]1[CH:13]=[C:12](B2OC(C)(C)C(C)(C)O2)[CH:11]=[N:10]1.Br[C:24]1[CH:25]=[C:26]([CH2:31][C:32]([O:34][CH3:35])=[O:33])[CH:27]=[CH:28][C:29]=1[F:30]>C(#N)C>[F:30][C:29]1[CH:24]=[CH:25][C:26]([CH2:31][C:32]([O:34][CH3:35])=[O:33])=[CH:27][C:28]=1[C:12]1[CH:11]=[N:10][N:9]([CH3:8])[CH:13]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Pd-118 (0.201 g) was dissolved in acetonitrile (20 mL) and stirred for 5 min before addition of potassium carbonate (5.34 g), water (20 mL) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.95 g). The mixture was stirred for a further 5 min then methyl 2-(3-bromo-4-fluorophenyl)acetate [Example 13, Step i)] (3.18 g) in MeCN (2 mL) added and the reaction was heated at the heating block (80° C.) for 25 min. The mixture was cooled and extracted into DCM (100 mL). Organic was separated, dried over magnesium sulfate. Solvents were evaporated to give a brown oil. The crude product was purified by flash silica chromatography, elution gradient 0 to 60% ethyl acetate in isohexane to afford the subtitled compound (3.36 g) as a gum. 1H NMR (300 MHz, CDCl3) δ 7.84 (s, 1H), 7.77 (d, J=2.3 Hz, 1H), 7.44 (dd, J=7.3, 1.5 Hz, 1H), 7.12-7.02 (m, 2H), 3.96 (s, 3H), 3.71 (s, 3H), 3.62 (s, 2H)

Workup

temperatureThe mixture was cooled
extractionextracted into DCM (100 mL)
customOrganic was separated
dry with materialdried over magnesium sulfate
customSolvents were evaporated
customto give a brown oil
customThe crude product was purified by flash silica chromatography, elution gradient 0 to 60% ethyl acetate in isohexane

Sources & evidence

ORD record: ord-4c719241ec244ca0a5d072516891fc73
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08017602B2

Reaction notes

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