tert-Butanol → HCID 68736815, compound

HRID 220423Notes

Reaction equation

HRID 220423 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)=[N:6][CH:5]=[CH:4][N:3]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[Na].CC(O)(C)C>C1(C)C=CC=CC=1.C(OCC)C.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:2]2[C:7]([C:8]3[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=3)=[N:6][CH:5]=[CH:4][N:3]=2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

9

Reactant 5

HCID 6386tert-ButanolHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 5360545SodiumHCID 131998892-Chloro-3-(4-chlorophenyl)pyrazine

Product 1

HCID 68736815HCID 68736815, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

Couple 2-chloro-3-(4-chlorophenyl)-pyrazine (0.148 g, 0.710 mmol) and piperazine-1-carboxylic acid t-butyl ester (0.216 g, 1.16 mmol), using 2-(dicyclohexylphosphino)biphenyl (0.0321 g, 0.0916 mmol), tris(dibenzylideneacetone) dipalladium (0.0328 g, 0.0388 mmol), and the sodium salt of 2-methylpropan-2-ol (0.104 g, 1.09 mmol) in toluene (9 mL) at 82° C. for 17 hr. Cool the reaction to room temperature, dilute with diethyl ether (50 mL), filter through a 1 cm pad of silica gel, rinse the pad with diethyl ether (2×25 mL), combine the organic solutions, concentrate and purify (silica gel chromatography, eluting with 0:100 to 1:1 ethyl acetate:hexanes) to give 3′-(4-chloro-phenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.143 g, 56%). MS (ES): m/z=303 [M+H-isobutylene]+.

Workup

  1. temperatureCool
  2. customthe reaction to room temperature
  3. filtrationfilter through a 1 cm pad of silica gel
  4. washrinse the pad with diethyl ether (2×25 mL)
  5. concentrationconcentrate
  6. custompurify
  7. wash(silica gel chromatography, eluting with 0:100 to 1:1 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-865df7d8a78a488595236858ba547341
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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