1,4-Dibromobenzene → (3aR,6aR)-1-(4-Bromophenyl)-5-methyloctahydropyrrolo[3,4-b]pyrrole

HRID 912485

Reaction equation

HRID 912485 reaction equation
[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([NH:5][CH2:6][CH2:7]2)[CH2:3]1.[Br:10][C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:10][C:11]1[CH:16]=[CH:15][C:14]([N:5]2[CH2:6][CH2:7][C@@H:8]3[CH2:9][N:2]([CH3:1])[CH2:3][C@H:4]23)=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 78041,4-DibromobenzeneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 44221716(3aR,6aR)-5-Methyloctahydropyrrolo[3,4-b]pyrrole

Product 1

HCID 44221503(3aR,6aR)-1-(4-Bromophenyl)-5-methyloctahydropyrrolo[3,4-b]pyrrole

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

The product of Example A7 (2.30 g, 18.2 mmole), 1,4-dibromobenzene (5.16 g, 20.9 mmole), tris(dibenzylideneacetone)dipalladium (340 mg, 0.36 mmole), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (460 mg, 0.73 mmole) and sodium tert-butoxide (2.63 g, 27.3 mmole) were dissolved in 20 ml of toluene and heated to 70° C. under N2 for 16 hours. The mixture was cooled to room temperature, diluted with water and extracted with dichloromethane (5×). The combined organics were dried over sodium sulfate, filtered and concentrated and purified by chromatography (eluting with a mixture of 5% MeOH in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.25-7.30 (m, 2 H) 6.41-6.46 (m, 2 H) 4.07 (m, 1 H) 3.47 (ddd, J=9.1, 7.7, 5.9 Hz, 1 H) 3.19 (dt, J=8.9, 7.3 Hz, 1 H) 2.95 (m, 1 H) 2.68 (dd, J=9.0, 3.0 Hz, 1 H) 2.55-2.60 (m, 3 H) 2.32 (s, 3 H) 2.13-2.22 (m, 1 H) 1.88-1.98 (m, 1 H). MS: (M+H)+=281/283.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with dichloromethane (5×)
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by chromatography (
  7. washeluting with a mixture of 5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-6c66c04f59564d119c6d0595fb44c6ed
Source dataset
uspto-grants-2011_09
Patent number
US08026240B2

Linked notes

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