Water → 2-(5-[1,3]Dioxolan-2-yl-2,4-dimethoxy-phenyl)-pyrazine

HRID 10664

Reaction equation

HRID 10664 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[C:7]([O:23][CH3:24])=[CH:8][C:9]([O:21][CH3:22])=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:11]=1.I[C:26]1[CH:31]=[N:30][CH:29]=[CH:28][N:27]=1.C([O-])([O-])=O.[Na+].[Na+].O>COCCOC.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>[O:3]1[CH2:4][CH2:5][O:1][CH:2]1[C:6]1[C:7]([O:23][CH3:24])=[CH:8][C:9]([O:21][CH3:22])=[C:10]([C:26]2[CH:31]=[N:30][CH:29]=[CH:28][N:27]=2)[CH:11]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 642841IodopyrazineHCID 161156182-(5-(1,3-Dioxolan-2-yl)-2,4-dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 219809982-(5-[1,3]Dioxolan-2-yl-2,4-dimethoxy-phenyl)-pyrazineYield 59%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Ex-46C: 2-(5-[1.3]Dioxolan-2-yl-2,4-dimethoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Ex-46B, 2.22 g, 6.60 mmol, containing borolane impurity) was dissolved in DME (60 mL) and 2-iodopyrazine (0.59 mL, 6.0 mmol) was added. 2M aqueous Na2CO3 (17.8 mL, 35.6 mmol) was added and the mixture was purged with nitrogen for 20 min. Tetrakis(triphenylphosphine)palladium(0) (0.69 g, 0.60 mmol) was added and the mixture was heated at reflux for 2.5 h. After cooling, water (50 mL) was added and the mixture was extracted with CH2Cl2 (2×30 mL). The organic phase was washed with brine (1×20 mL), dried over sodium sulfate, filtered, and concentrated. Purification of the resulting yellow-orange solids via silica chromatography (50–80% EtOAc/hexanes) provided 1.02 g of 2-(5-[1,3]dioxolan-2-yl-2,4-dimethoxy-phenyl)-pyrazine as a yellow solid (59% yield). 1H-NMR (CDCl3) δ 9.10 (d, J=2 Hz, 1H), 8.61 (m, 1H), 8.39 (d, J=3 Hz, 1H), 8.07 (s, 1H), 6.57 (s, 1H), 6.14 (s, 1H), 4.13–4.18 (m, 2H), 4.01–4.05 (m, 2H), 3.95 (s, 3H), 3.93 (s, 3H).

Workup

  1. customthe mixture was purged with nitrogen for 20 min
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 2.5 h
  4. temperatureAfter cooling
  5. extractionthe mixture was extracted with CH2Cl2 (2×30 mL)
  6. washThe organic phase was washed with brine (1×20 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the resulting yellow-orange solids via silica chromatography (50–80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1c1ac17fdab24ec4b251ad30815eb2e7
Source dataset
uspto-grants-2006_08
Patent number
US07094801B2

Linked notes

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