Dichloromethane → Cyclopentanecarboxylic acid, 2-[(4'-amino[1,1'-biphenyl]-4-yl)carbonyl]-, methyl ester, (1R,2R)-

HRID 30863Notes

Reaction equation

HRID 30863 reaction equation
Br[C:2]1[CH:18]=[CH:17][C:5]([C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[C:13]([O:15][CH3:16])=[O:14])=[O:7])=[CH:4][CH:3]=1.[NH2:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=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>[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[CH:18]=[CH:17][C:5]([C:6]([C@@H:8]3[CH2:12][CH2:11][CH2:10][C@H:9]3[C:13]([O:15][CH3:16])=[O:14])=[O:7])=[CH:4][CH:3]=2)=[CH:22][CH:21]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27346154-Aminophenylboronic acidHCID 58681296(1R,2R)-Methyl 2-(4-bromobenzoyl)cyclopentanecarboxylate

Product 1

HCID 11416053Cyclopentanecarboxylic acid, 2-[(4'-amino[1,1'-biphenyl]-4-yl)carbonyl]-, methyl ester, (1R,2R)-Yield 67.4%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

Methyl trans-2-(4-bromobenzoyl)cyclopentanecarboxylate (1.60 g, 5.14 mmol) and 4-aminophenyl boronic acid (1.07 g, 6.17 mmol) were combined in a dry flask under argon. Toluene (25 mL), EtOH (10 mL), and 3 M aqueous Na2CO3 (8.50 mL, 25 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 (419.9 mg, 0.51 mmol), was added and the resulting mixture was heated at 85° C. for 16 h. The mixture was cooled to rt, 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 29 to 33% ethyl acetate in hexane to afford methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]-cyclopentanecarboxylate (1.12 g, 67%). 1H NMR (400 MHz, CD2Cl2) δ 1.71-1.97 (m, 4H), 2.17 (m, 2H), 3.44 (m, 1H), 3.65 (s, 3H), 4.12 (m, 1H), 6.84 (m, 2H), 7.51 (m, 2H), 7.66 (m, 2H), 8.00 (m, 2H).

Workup

  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)

Sources & evidence

ORD record
ord-74f2ce73411e467f8d577e9b127a74fb
Source dataset
uspto-grants-2008_09
Patent number
US07423156B2

Reaction notes

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