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

HRID 9539

반응식

HRID 9539 반응식
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

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 702Ethanol용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
85 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-f28078c0604c469b887a017ec7139846
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091228B2

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