Diethyl Ether → tert-butyl (3aS,6aS)-5-(5-bromo-3-pyridinyl)hexahydropyrrolo[3,4-b]pyrrole-1(2H)-carboxylate

HRID 1816993Notes

Reaction equation

[N:1]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4][C@H:3]2[CH2:6][NH:7][CH2:8][C@@H:2]12.[Br:16][C:17]1[CH:18]=[N:19][CH:20]=[C:21](Br)[CH:22]=1.CC(C)([O-])C.[Na+].C(OCC)C>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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>[Br:16][C:17]1[CH:22]=[C:21]([N:7]2[CH2:6][C@H:3]3[C@H:2]([N:1]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]3)[CH2:8]2)[CH:20]=[N:19][CH:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

The product from Example 15E (0.56 g, 2.70 mmol) in toluene (27 mL) was treated with tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, available from Alfa Aesar) (50 mg, 0.10 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP, available from Strem Chemicals) (68 mg, 0.10 mmol), 3,5-dibromopyridine (available from Aldrich Chemical Co.,) (0.69 g, 2.90 mmol) and sodium tert-butoxide (available from Aldrich Chemical Co.,) (0.44 g, 4.60 mmol). After heating at 80° C. for 16 hours, the reaction mixture was poured into diethyl ether (100 mL), washed with brine (100 mL), dried (MgSO4) and concentrated under reduced pressure. The residue was purified by chromatography (SiO2, 5% MeOH/CH2Cl2) to provide the title compound as a yellow oil (0.47 g, 47% yield). MS (DCI/NH3) m/z 368/370 (M+H)+.

Workup

washwashed with brine (100 mL)
dry with materialdried (MgSO4)
concentrationconcentrated under reduced pressure
customThe residue was purified by chromatography (SiO2, 5% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-da7e5fb95a374235af01c0f9a3d87abc
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07598236B2

Reaction notes

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