4-(3-Hydroxypropyl)Benzeneboronic Acid → 1-(4-chlorobenzyl)-5-(4-(3-hydroxypropyl)phenyl)pyridin-2(1H)-one

HRID 1948190Notes

Reaction equation

HRID 1948190 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH:12]=[C:11](Br)[CH:10]=[CH:9][C:8]2=[O:14])=[CH:4][CH:3]=1.[OH:17][CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1>O1CCOCC1.CCOC(C)=O.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>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH:12]=[C:11]([C:24]3[CH:25]=[CH:26][C:21]([CH2:20][CH2:19][CH2:18][OH:17])=[CH:22][CH:23]=3)[CH:10]=[CH:9][C:8]2=[O:14])=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 51513424-(3-Hydroxypropyl)Benzeneboronic AcidHCID 603727735-Bromo-1-[(4-chlorophenyl)methyl]-1,2-dihydropyridin-2-one

Product 1

HCID 589669411-(4-chlorobenzyl)-5-(4-(3-hydroxypropyl)phenyl)pyridin-2(1H)-oneYield 66.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

According to Scheme 3 Method A: To a solution of 1-(4-chlorobenzyl)-5-bromopyridin-2(1H)-one (1 eq, 0.33 mmol, 0.10 g) in dioxane/saturated aqueous NaHCO3 (1:1, 6 mL) was added Pd(PPh3)4 (0.15 eq, 0.05 mmol, 58 mg) and 4-(3-hydroxypropyl)phenylboronic acid (1.5 eq, 0.50 mmol, 90.0 mg). The reaction was then stirred at 90° C. for 4.5 hours. The reaction was allowed to cool and diluted with AcOEt. The reaction washed with saturated NH4Cl solution, brine and the organic phase extracted (×3). The combined organic fractions were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel (AIT Flashsmart prepacked column 15 g SiO2) using pure AcOEt as the eluent to afford 1-(4-chlorobenzyl)-5-(4-(3-hydroxypropyl)phenyl)pyridin-2(1H)-one (0.22 mmol, 78 mg, 66%) as a white solid. M.p.: 165° C.; Rf=0.05 (CH2Cl2/AcOEt 80/20); LC (XTerra RP18, 3.5 μm, 3.0×50 mm Column): RT=3.78 min; MS m/z (CI) [MH]+=354, 356; 1H NMR (300 MHz, DMSO-d6) δ 1.64-1.77 (m, 2H), 2.61 (t, J=7.3 Hz, 2H), 3.32-3.46 (m, 2H), 4.48 (t, J=5.1 Hz, 1H), 5.15 (s, 2H), 6.52 (d, J=9.5 Hz, 1H), 7.24 (d, J=8.1 Hz, 2H), 7.35-7.44 (4H), 7.47 (d, J=8.1 Hz, 2H), 7.83 (dd, J=2.6 Hz, 9.5 Hz, 1H), 8.23 (d, J=2.6 Hz, 1H).

Workup

  1. temperatureto cool
  2. washThe reaction washed with saturated NH4Cl solution, brine
  3. extractionthe organic phase extracted (×3)
  4. dry with materialThe combined organic fractions were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by flash chromatography over silica gel (AIT Flashsmart prepacked column 15 g SiO2)

Sources & evidence

ORD record
ord-9f3dc67b2b34408283cd52d842d20387
Source dataset
uspto-grants-2013_03
Patent number
US08399493B2

Reaction notes

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