Binap, (A+-)- → (3aR,6aS)-tert-butyl 5-(5-(2-methylbenzylcarbamoyl)pyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

HRID 240501Notes

Reaction equation

HRID 240501 reaction equation
[CH2:1]1[C@@H:5]2[CH2:6][NH:7][CH2:8][C@@H:4]2[CH2:3][N:2]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].Br[C:17]1[CH:18]=[N:19][CH:20]=[C:21]([CH:33]=1)[C:22]([NH:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH3:32])=[O:23].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>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].C1(C)C=CC=CC=1>[CH3:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[CH2:25][NH:24][C:22]([C:21]1[CH:33]=[C:17]([N:7]2[CH2:6][C@@H:5]3[CH2:1][N:2]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3][C@@H:4]3[CH2:8]2)[CH:18]=[N:19][CH:20]=1)=[O:23]

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 1514452Cis-2-boc-hexahydropyrrolo[3,4-C]pyrroleHCID 91046105-bromo-N-(2-methylbenzyl)nicotinamideHCID 23676156Sodium t-butoxide

Product 1

HCID 67265573(3aR,6aS)-tert-butyl 5-(5-(2-methylbenzylcarbamoyl)pyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylateYield 91%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

The product from Example 1C (80 mg, 0.38 mmol), the product from Example 31A (155 mg, 0.51 mmol), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (34 mg, 0.034 mmol), tris(dibenzylideneacetone)dipalladium(0) (10.4 mg, 0.011 mmol), and sodium tert-butoxide (54.2 mg, 0.054 mmol) were combined with toluene (5 mL). The suspension was evacuated and purged with nitrogen. The mixture was heated at 95° C. under nitrogen for 4 h. The residue was partitioned between saturated sodium bicarbonate solution(aq) (100 mL) and EtOAc (2×50 mL). The combined organic extract was washed with brine (100 mL), dried (Na2SO4) and concentrated under vacuum. The residue was purified by flash chromatography (eluted with EtOAc) on silica to provide the title compound (150 mg, 91%). MS (APCI) m/z 437 (M+H)+.

Workup

  1. customThe suspension was evacuated
  2. custompurged with nitrogen
  3. customThe residue was partitioned between saturated sodium bicarbonate solution(aq) (100 mL) and EtOAc (2×50 mL)
  4. extractionThe combined organic extract
  5. washwas washed with brine (100 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by flash chromatography (eluted with EtOAc) on silica

Sources & evidence

ORD record
ord-4dc86f119fa7405ba7b15e51178a5204
Source dataset
uspto-grants-2014_02
Patent number
US08648084B2

Reaction notes

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