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

HRID 220439

反応式

HRID 220439 の反応式
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[C:3]=1[F:12].CC1(C)COB(B2OCC(C)(C)CO2)OC1.C([O-])(=O)C.[K+].[C:34]([O:38][C:39]([N:41]1[CH2:46][CH2:45][N:44]([C:47]2[C:52](Cl)=[N:51][CH:50]=[CH:49][N:48]=2)[CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O.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]>[C:34]([O:38][C:39]([N:41]1[CH2:46][CH2:45][N:44]([C:47]2[C:52]([C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[C:3]=3[F:12])=[N:51][CH:50]=[CH:49][N:48]=2)[CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:35])[CH3:36]

参加物

9

反応物 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 27363203-Bromo-2-fluorobenzotrifluorideHCID 11150691Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate

生成物 1

HCID 687379823'-(2-Fluoro-3-trifluoromethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid t-butyl ester収率 18%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

Combine 1-bromo-2-fluoro-3-trifluoromethylbenzene (0.424 g, 1.77 mmol), 5,5,5′,5′-tetramethyl-[2,2′]bi[1,3,2]dioxaborinanyl] (0.458 g, 2.03 mmol), 1,1′-bis(diphenylphosphino)ferrocene dichloropalladium (0.0632 g, 0.0774 mmol), and potassium acetate (0.499 g, 5.08 mmol) in DMF (10 mL), and purge with nitrogen for 0.5 hr. Heat for 2 hr. at 80° C. and cool to room temperature. Add 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.406 g, 1.36 mmol), sodium carbonate (4.0 mL of a 2M solution in water,) and bis(diphenylphosphino)ferrocene dichloropalladium (0.052 g, 0.0638 mmol). Heat the reaction at 80° C. for 20 hr. Purify by silica gel chromatography, eluting with 5:95 to 40:60 ethyl acetate:hexanes to give the 3′-(2-fluoro-3-trifluoromethyl-phenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.102 g, 18%).

後処理

  1. temperatureHeat for 2 hr
  2. temperatureHeat
  3. customthe reaction at 80° C. for 20 hr
  4. customPurify by silica gel chromatography
  5. washeluting with 5:95 to 40:60 ethyl acetate

出典と根拠

ORDレコード
ord-0a55424dfb37488fb681ea8c118bc369
出典データセット
uspto-grants-2012_06
特許番号
US08202873B2

関連ノート

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