Sodium Carbonate → 3-([1-(Tert-butoxycarbonyl)piperidin-4-ylidene]{4-[(diethylamino)carbonyl]phenyl}methyl)benzoic acid

HRID 1271675Notes

Reaction equation

HRID 1271675 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[C:14](Br)[C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:27])[N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:29]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)([OH:31])=[O:30].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:23]([N:22]([CH2:25][CH3:26])[C:21](=[O:27])[C:18]1[CH:19]=[CH:20][C:15]([C:14](=[C:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[C:36]2[CH:35]=[CH:34][CH:33]=[C:32]([C:29]([OH:31])=[O:30])[CH:37]=2)=[CH:16][CH:17]=1)[CH3:24]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27339573-Carboxyphenylboronic acidHCID 10503756HCID 10503756, compound

Product 1

HCID 184529743-([1-(Tert-butoxycarbonyl)piperidin-4-ylidene]{4-[(diethylamino)carbonyl]phenyl}methyl)benzoic acidYield 70%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-[bromo-(4-diethylcarbamoyl-phenyl)-methylene]-piperidine-1-carboxylic acid tert-butyl ester (1a, 451 mg, 1.0 mmol), 3-carboxyphenyl boronic acid (330 mg, 2.0 mmol), 2M Na2CO3 (3 mL), and tetrakis(triphenyl phosphine) palladium(0) (25 mg) in toluene (degassed, 10 mL) and ethanol (degassed, 10 mL) was refluxed at 90° C. for 4 hrs under N2. The reaction mixture was then quenched with aqueous NH4Cl after cooling down to 0° C., and extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine, dried over MgSO4, and evaporated to give a crude product, which was purified by flash silica gel column to provide the desired compound 2a (345 mg, 70%): 1H NMR (CDCl3) δ 1.15 (3 H, br m, CH3CH2—), 1.23 (3 H, br m, CH3CH2—), 1.47 (9 H, s, C(CH3)3), 2.31 (2 H, m, piperidine CH—), 2.35 (2 H, m, piperidine CH—), 3.30 (2 H, br m, CH3CH2N—), 3.48 (4 H, m, piperidine CH—), 3.54 (2 H, br m, CH3CH2N—), 7.14 (2 H, d, J=8.0 Hz, ArH), 7.24 (1 H, m, ArH), 7.33 (2 H, d, J=8.0 Hz, ArH), 7.42 (1 H, t, J=7.6 Hz, ArH), 7.86(1 H, s, ArH), 7.97 (1 H, d, J=7.6 Hz, ArH). IR (NaCl)2976, 1718, 1691, 1598, 1430, 1233, 1166 cm−1.

Workup

  1. customThe reaction mixture was then quenched with aqueous NH4Cl
  2. temperatureafter cooling down to 0° C.
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customto give a crude product, which
  8. customwas purified by flash silica gel column

Sources & evidence

ORD record
ord-44885e574756455cb0d3f58c8873b540
Source dataset
uspto-grants-2007_04
Patent number
US07205317B2

Reaction notes

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