4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (4-{4-[4-(1H-pyrazol-4-yl)-phenyl]-piperidin-4-yl}-phenoxy)-acetic acid

HRID 45549Notes

Reaction equation

HRID 45549 reaction equation
C([O:3][C:4](=[O:26])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2([C:19]3[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=3)[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[CH:9][CH:8]=1)C.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[N:37][NH:38][CH:39]=2)O1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:37]1[CH:36]=[C:35]([C:22]2[CH:21]=[CH:20][C:19]([C:13]3([C:10]4[CH:9]=[CH:8][C:7]([O:6][CH2:5][C:4]([OH:3])=[O:26])=[CH:12][CH:11]=4)[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[CH:24][CH:23]=2)[CH:39]=[N:38]1

Participants

4

Reactant 2

HCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 59331921HCID 59331921, compound

Product 1

HCID 11349421(4-{4-[4-(1H-pyrazol-4-yl)-phenyl]-piperidin-4-yl}-phenoxy)-acetic acidYield 5%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

{4-[4-(4-bromo-phenyl)-piperidin-4-yl]-phenoxy}-acetic acid ethyl ester was reacted with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole following the procedure set out in Example 1, but using tetrakis(triphenylphosphine)palladium (0) as the catalyst and heating at 80° C. for 30 minutes, to yield a mixture of the title compounds. On work up the basic aqueous extract was neutralised with hydrochloric acid and extracted with ethyl acetate (×2), then these organic extracts were combined and washed with brine, dried (MgSO4), filtered and concentrated to give a crude product that was recrystallised from water to afford (4-{4-[4-(1H-pyrazol-4-yl)-phenyl]-piperidin-4-yl}-phenoxy)-acetic acid (12 mg, 5%); LCMS (PS-A3) Rt 5.33 min [M+H]+ 378. 1H NMR (DMSO-d6) δ 2.22-2.26 (4H, m), 2.67-2.71 (4H, m), 4.65 (2H, s) 6.67 (2H, d), 7.11 (2H, d), 7.24 (2H, d), 7.46 (2H, d), 7.96 (2H, br.s).

Workup

  1. customto yield
  2. extractionOn work up the basic aqueous extract
  3. extractionextracted with ethyl acetate (×2)
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude product that
  9. customwas recrystallised from water

Sources & evidence

ORD record
ord-0e7aa5daa3834c7d85a058b0f5a3b823
Source dataset
uspto-grants-2013_09
Patent number
US08541461B2

Reaction notes

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