Sodium Carbonate → 1-(2-Hydroxyethyl)-5-(4-methylthiophen-2-yl)pyrazin-2(1H)-one

HRID 1878765Notes

Reaction equation

HRID 1878765 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5](=[O:11])[N:6]([CH2:8][CH2:9][OH:10])[CH:7]=1.[CH3:12][C:13]1[CH:14]=[C:15](B(O)O)[S:16][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:10][CH2:9][CH2:8][N:6]1[CH:7]=[C:2]([C:15]2[S:16][CH:17]=[C:13]([CH3:12])[CH:14]=2)[N:3]=[CH:4][C:5]1=[O:11]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343734-Methylthiophene-2-boronic acidHCID 598431015-Bromo-1-(2-hydroxyethyl)pyrazin-2(1H)-one

Product 1

HCID 598430841-(2-Hydroxyethyl)-5-(4-methylthiophen-2-yl)pyrazin-2(1H)-oneYield 51.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

5-Bromo-1-(2-hydroxyethyl)pyrazin-2(1H)-one (199.6 mg, 911 μmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (66.6 mg, 91 μmol), and 4-methylthiophen-2-ylboronic acid (253.7 mg, 1787 μmol) were suspended in DME (5.0 mL) and sodium carbonate (1.2 mL, 2.0 M in water, 2.4 mmol) was added. The reaction flask was fit with a reflux condensor and placed in a preheated oil bath (85° C.) and stirred under argon for 1 hour The reaction was then cooled to room temperature and quenched with saturated sodium bicarbonate (5 mL) and allowed to stand at room temperature overnight. It was then extracted with CH2Cl2 and with 10:1 CH2Cl2/MeOH, and the organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and filtered through silica gel (30:1 CH2Cl2/MeOH) to afford the desired product (110.6 mg, 0.468 mmol, 51% yield). MS (ESI pos. ion) m/z (MH+): 237. Calc'd exact mass for C11H12N2O2S: 236. 1H NMR (400 MHz, CDCl3): 8.21 (s, 1H), 7.53 (s, 1H), 7.12 (s, 1H), 6.88 (s, 1H), 4.14 (t, J=5.0 Hz, 2H), 4.02 (q, J=5.0 Hz, 2H), 2.33 (s, 1H, J=5.0 Hz, 1H), 2.28 (s, 3H).

Workup

  1. customplaced in a preheated oil bath
  2. temperaturewas then cooled to room temperature
  3. customquenched with saturated sodium bicarbonate (5 mL)
  4. waitto stand at room temperature overnight
  5. extractionIt was then extracted with CH2Cl2 and with 10:1 CH2Cl2/MeOH
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. filtrationfiltered through silica gel (30:1 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-0a7e9277f68f4b249bc76b98a229dcba
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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