Water → HCID 59290460, compound

HRID 909928Notes

Reaction equation

HRID 909928 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[C:25]([F:42])=[C:26]([CH:39]=[CH:40][CH:41]=1)[CH2:27][CH2:28][O:29][CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>C(#N)C>[F:42][C:25]1[C:24]([C:12]2[CH:11]=[N:10][N:9]([CH3:8])[CH:13]=2)=[CH:41][CH:40]=[CH:39][C:26]=1[CH2:27][CH2:28][O:29][CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 592904361,1-Dimethylethyl 3-[2-(3-bromo-2-fluorophenyl)ethoxy]propanoate

Product 1

HCID 59290460HCID 59290460, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Pd-118 (104 mg) was dissolved in acetonitrile (10 mL) and stirred for 5 min before addition of potassium carbonate (2.364 g), water (10 mL) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.305 g). The mixture was stirred for a further 5 min then tert-butyl 3-(3-bromo-2-fluorophenethoxy)propanoate [Example 16, Step iii)] (1.98 g) added and the reaction was heated at the heating block (80° C.) for 2 h. The mixture was cooled and extracted into ethyl acetate (150 mL). Organic was separated, dried (MgSO4) solvents 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 (1.480 g) as a gum. MS [M+H-C4H9]+=293 (MultiMode+) 1H NMR (300 MHz, CDCl3) δ 7.83 (s, 1H), 7.75 (d, J=2.5 Hz, 1H), 7.39 (td, J=2.5 and 7.3 Hz, 1H), 7.13-7.01 (m, 2H), 3.96 (s, 3H), 3.74-3.64 (m, 4H), 2.96 (t, J=6.8 Hz, 2H), 2.49 (t, J=6.4 Hz, 2H), 1.44 (s, 9H).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted into ethyl acetate (150 mL)
  3. customOrganic was separated
  4. dry with materialdried (MgSO4) solvents
  5. customevaporated
  6. customto give a brown oil
  7. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 60% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-b6a86be701cf4ca685c792a2edb2f80d
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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