Dichloromethane → Methyl cis-2-[(4'-amino-1,1'-biphenyl-4-yl)carbonyl]cyclohexanecarboxylate

HRID 9539

反応式

HRID 9539 の反応式
Br[C:2]1[CH:19]=[CH:18][C:5]([C:6]([C@H:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]2[C:14]([O:16][CH3:17])=[O:15])=[O:7])=[CH:4][CH:3]=1.[NH2:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C([O-])([O-])=O.[Na+].[Na+].ClCCl>CCOC(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].CCO.C1(C)C=CC=CC=1>[NH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:19]=[CH:18][C:5]([C:6]([C@H:8]3[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]3[C:14]([O:16][CH3:17])=[O:15])=[O:7])=[CH:4][CH:3]=2)=[CH:23][CH:22]=1

参加物

9

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27346154-Aminophenylboronic acidHCID 67147291Methyl cis-2-(4-bromobenzoyl)cyclohexanecarboxylate

生成物 1

HCID 67147298Methyl cis-2-[(4'-amino-1,1'-biphenyl-4-yl)carbonyl]cyclohexanecarboxylate

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

Methyl cis-2-(4-bromobenzoyl)cyclohexanecarboxylate (1.76 g, 5.41 mmol) and 4-amino phenyl boronic acid (1.13 g, 6.49 mmol) were added to a clean dry flask under argon. Toluene (50 mL), EtOH (20 mL), and 3 M aqueous Na2CO3 (14 mL, 43 mmol) were added, and resulting solution was degassed for 30 minutes by using a flow of argon. Then [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II), 1:1 complex with dichloromethane (442 mg, 0.54 mmol) was added and the resulting mixture was heated at 85° C. for 16 h. The mixture was cooled to rt, and then diluted with EtOAc and passed through a Celite® pad. The solvent was removed by rotary evaporation. Water and EtOAc were added, and the aqueous layer was extracted with EtOAc. The combined organic phases were washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (Biotage Flash 40M) using 33 to 40% ethyl acetate in hexane to afford methyl cis-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclohexanecarboxylate.(1.54 g, 84%). LC-MS ret. time 3.99; m/z 338 (MH+); 1H NMR (400 MHz, CD2Cl2) δ 1.37–1.53 (m, 3H), 1.74–1.88 (m, 2H), 1.90–1.99 (m, 1H), 2.04–2.22 (m, 2H), 2.75 (m, 1H), 3.59 (s, 3H), 3.90 (q, 1H), 6.79 (m, 2H), 7.48 (m, 2H), 7.63 (m, 2H), 7.89 (m, 2H).

後処理

  1. customresulting solution
  2. customwas degassed for 30 minutes
  3. temperatureThe mixture was cooled to rt
  4. customThe solvent was removed by rotary evaporation
  5. additionWater and EtOAc were added
  6. extractionthe aqueous layer was extracted with EtOAc
  7. washThe combined organic phases were washed with water, brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography (Biotage Flash 40M)

出典と根拠

ORDレコード
ord-f28078c0604c469b887a017ec7139846
出典データセット
uspto-grants-2006_08
特許番号
US07091228B2

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