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

HRID 220434Notes

Reaction equation

HRID 220434 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].[CH:21]([O:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)([CH3:23])[CH3:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC.O.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:28]3[CH:29]=[CH:30][C:25]([O:24][CH:21]([CH3:23])[CH3:22])=[CH:26][CH:27]=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 36987264-Isopropoxybenzeneboronic acidHCID 11150691Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate

Product 1

HCID 687371373'-(4-Isopropoxyphenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid t-butyl esterYield 80%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 10311-PropanolSolvent

Procedure

Couple 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.135 g, 0.452 mmol) and 4-isopropoxyphenylboronic acid (0.134 g, 0.743 mmol), in the presence of triphenylphosphine (0.0482 g, 0.184 mmol), palladium acetate (0.0118 g, 0.0526 mmol), aqueous 2 N sodium carbonate (0.3 mL) in a mixture of n-propanol (4 mL) and water (0.3 mL). Reflux for 17.5 hr.s, cool to room temperature and extract with DCM. Purify by silica gel chromatography, eluting with 0:100 to 1:1 ethyl acetate:hexanes, to give 3′-(4-isopropoxyphenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.144 g, 80%).

Workup

  1. temperatureReflux for 17.5 hr
  2. extractionextract with DCM
  3. customPurify by silica gel chromatography
  4. washeluting with 0:100 to 1:1 ethyl acetate

Sources & evidence

ORD record
ord-a6398c2da2ec401db3af4d39f9694be8
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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