3,5-Dibromopyridine → (3aR,6aS)-tert-butyl 5-(5-bromopyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

HRID 240499Notes

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:16][C:17]1[CH:18]=[N:19][CH:20]=[C:21](Br)[CH:22]=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].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[Br:16][C:17]1[CH:22]=[C:21]([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:20]=[N:19][CH:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

The product from Example 1C (1.01 g, 4.76 mmol) and 3,5-dibromopyridine (1.22 g, 5.15 mmol) were dissolved in toluene (20 mL). Pd2(dba)3 (86.8 mg, 0.095 mmol), BINAP (175.0 mg, 0.28 mmol) and sodium tert-butoxide (665.4 mg, 1.460 mmol) were added to the reaction mixture. The reaction was heated to 80° C. for 22 h, then allowed to cool to ambient temperature, diluted with water (100 mL) and extracted with CH2Cl2 (3×100 mL). The organic extracts were combined and washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography (EtOAc, Rf=0.33) to afford the title compound as a white solid (1.17 g, 67%). MS (DCI/NH3) m/z 370 (M+H)+.

Workup

temperatureto cool to ambient temperature
extractionextracted with CH2Cl2 (3×100 mL)
washwashed with brine (50 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated under vacuum
customThe residue was purified by silica gel chromatography (EtOAc, Rf=0.33)

Sources & evidence

ORD record: ord-bc45a253e46b4974b20a230d5b57e4b4
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08648084B2

Reaction notes

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