Water → tert-Butyl 3-(3-(1-propyl-1H-pyrazol-4-yl)phenethoxy)propanoate

HRID 909931Notes

Reaction equation

HRID 909931 reaction equation
C(=O)([O-])[O-].[K+].[K+].O.[CH2:8]([N:11]1[CH:15]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:13]=[N:12]1)[CH2:9][CH3:10].Br[C:26]1[CH:27]=[C:28]([CH:41]=[CH:42][CH:43]=1)[CH2:29][CH2:30][O:31][CH2:32][CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35]>C(#N)C>[CH2:8]([N:11]1[CH:15]=[C:14]([C:26]2[CH:27]=[C:28]([CH:41]=[CH:42][CH:43]=2)[CH2:29][CH2:30][O:31][CH2:32][CH2:33][C:34]([O:36][C:37]([CH3:39])([CH3:40])[CH3:38])=[O:35])[CH:13]=[N:12]1)[CH2:9][CH3:10]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27604871-Propyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67075913HCID 67075913, compound

Product 1

HCID 59290411tert-Butyl 3-(3-(1-propyl-1H-pyrazol-4-yl)phenethoxy)propanoateYield 105.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
80 °C

Procedure

Pd-118 (51.7 mg) was dissolved in acetonitrile (8 mL) and stirred for 5 min before addition of potassium carbonate (1.1 g), water (8 mL) and a solution of 1-propyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (750 mg) in MeCN (1 mL). The mixture was stirred for a further 5 min then a solution of tert-butyl 3-(3-bromophenethoxy)propanoate (870 mg, prepared as in Preparation 3, Step i)) was added and the reaction was heated at the heating block (80° C.) for 30 min. The mixture was cooled and extracted into DCM. Organic was separated using a phase separator cartridge, solvents evaporated to give a brown oil. The crude product was purified by flash silica chromatography using elution gradient 0 to 100% ethyl acetate in isohexane to afford the subtitled compound (1 g) as a gum. MS [M+H-C4H9]+=303 (MultiMode+) 1H NMR (400 MHz, CDCl3) δ 7.76 (s, 1H), 7.63 (s, 1H), 7.34-7.30 (m, 2H), 7.26 (t, J=8.0 Hz, 1H), 7.09-7.05 (m, 1H), 4.11 (t, J=7.2 Hz, 2H), 3.70 (t, J=6.5 Hz, 2H), 3.68 (t, J=7.2 Hz, 2H), 2.89 (t, J=7.2 Hz, 2H), 2.49 (t, J=6.4 Hz, 2H), 1.93 (sextet, J=7.2 Hz, 2H), 1.43 (s, 9H), 0.95 (t, J=7.3 Hz, 3H)

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted into DCM
  3. customOrganic was separated
  4. customevaporated
  5. customto give a brown oil
  6. customThe crude product was purified by flash silica chromatography
  7. washelution gradient 0 to 100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-38aa9de459524fb9b892b563361c5e7f
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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