Sodium Carbonate → 1-(2-hydroxyethyl)-5-phenylpyrimidin-2(1H)-one

HRID 1878769Notes

Reaction equation

HRID 1878769 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5](=[O:11])[N:6]([CH2:8][CH2:9][OH:10])[CH:7]=1.[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[OH:10][CH2:9][CH2:8][N:6]1[CH:7]=[C:2]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:3]=[N:4][C:5]1=[O:11]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 204942745-Bromo-1-(2-hydroxyethyl)pyrimidin-2(1H)-one

Product 1

HCID 598429971-(2-hydroxyethyl)-5-phenylpyrimidin-2(1H)-oneYield 70.5%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
75 °C

Procedure

To a 10 mL round bottomed flask was added 5-bromo-1-(2-hydroxyethyl)pyrimidin-2(1H)-one (0.088 g, 0.40 mmol), phenylboronic acid (0.098 g, 0.80 mmol), 1,2-dimethoxyethane (2.5 mL) and 2 M sodium carbonate (0.40 mL, 0.80 mmol). The mixture was carefully evacuated and backfilled with N2. This was repeated twice. To the mixture was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II)dichloromethane adduct (0.029 g, 0.040 mmol). The mixture was again carefully evacuated and backfilled with N2. This was repeated once. The mixture was then heated at 75° C. for 1.5 hours. After cooling to room temperature, the mixture was poured into water (50 mL) and then extracted with EtOAc (2×) and then with 25% iPrOH/CHCl3 (3×). The combined extracts were washed with brine (1×), dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (0 to 2% MeOH (2M NH3)/CH2Cl2) afforded 1-(2-hydroxyethyl)-5-phenylpyrimidin-2(1H)-one (0.061 g, 70% yield) as an off-white solid. MS (ESI, pos. ion.) m/z: 217 (MH+). Calc'd exact mass for C12H12N2O2: 216. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.71 (q, J=5.3 Hz, 2 H), 4.00 (t, J=5.3 Hz, 2 H), 4.95 (t, J=5.6 Hz, 1 H), 7.35 (t, J=7.3 Hz, 1 H), 7.46 (t, J=7.6 Hz, 2 H), 7.61 (d, J=7.4 Hz, 2 H), 8.44 (d, J=3.3 Hz, 1 H), 8.95 (d, J=3.3 Hz, 1 H).

Workup

  1. customThe mixture was carefully evacuated
  2. customThe mixture was again carefully evacuated
  3. temperatureAfter cooling to room temperature
  4. additionthe mixture was poured into water (50 mL)
  5. extractionextracted with EtOAc (2×)
  6. washThe combined extracts were washed with brine (1×)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated onto silica
  9. customPurification by silica gel chromatography (0 to 2% MeOH (2M NH3)/CH2Cl2)

Sources & evidence

ORD record
ord-0eb8088da0e44356bb7d33023dc85531
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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