Sodium Carbonate → 3'-(4-Ethoxyphenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid t-butyl ester

HRID 220432Notes

Reaction equation

HRID 220432 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19](Cl)=[N:18][CH:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:21]([O:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)[CH3:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([C:27]3[CH:28]=[CH:29][C:24]([O:23][CH2:21][CH3:22])=[CH:25][CH:26]=3)=[N:18][CH:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27343514-Ethoxyphenylboronic acidHCID 11150691Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate

Product 1

HCID 687387893'-(4-Ethoxyphenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid t-butyl esterYield 191.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

Couple 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.726 g, 2.43 mmol) and 4-ethoxyphenylboronic acid (0.95 g, 5.991 mmol), in the presence of triphenylphosphine (0.202 g, 0.770 mmol), palladium acetate (0.056 g, 0.243 mmol), sodium carbonate (3.8 mL of a 2 N solution in water) in a mixture of acetonitrile (42 mL) and water (8 mL). Reflux for 3 hr. Purify by silica gel chromatography, eluting with 0:100 to 25:75 ethyl acetate:hexanes, to give 3′-(4-ethoxyphenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (1.79 g, 96%).

Workup

  1. temperatureReflux for 3 hr
  2. customPurify by silica gel chromatography
  3. washeluting with 0:100 to 25:75 ethyl acetate

Sources & evidence

ORD record
ord-a29f0350fe5143cda44a4d28bc914b64
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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