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

HRID 2251427Notes

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-09ed091254c949b8bdf8bf6b789f2048
Source dataset: uspto-grants-2008_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07319106B2

Reaction notes

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