Cesium carbonate → tert-Butyl 5-(5-ethoxycarbonylpyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

HRID 1697449Notes

Reaction equation

HRID 1697449 reaction equation
[CH2:1]1[CH:5]2[CH2:6][NH:7][CH2:8][CH: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:27]=1)[C:22]([O:24][CH2:25][CH3:26])=[O:23].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[CH2:25]([O:24][C:22]([C:21]1[CH:27]=[C:17]([N:7]2[CH2:6][CH:5]3[CH2:1][N:2]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3][CH:4]3[CH2:8]2)[CH:18]=[N:19][CH:20]=1)=[O:23])[CH3:26]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 140785Ethyl 5-bromopyridine-3-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4142526Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylate

Product 1

HCID 67265660tert-Butyl 5-(5-ethoxycarbonylpyridin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A suspension of tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1 H)-carboxylate (2.00 g, 9.42 mmol; see Schrimpf, Michael R.; Tietje, Karin R.; Toupence, Richard B.; Ji, Jianguo; Basha, Anwer; Bunnelle, William H.; Daanen, Jerome F.; Pace, Jennifer M.; Sippy, Kevin B. WO 2001081347), ethyl 5-bromonicotinate (2.80 g, 12.0 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium(0) (259 mg, 0.283 mmol; Strem), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (491 mg, 0.848 mmol; Aldrich) and cesium carbonate (4.91 g, 15.1 mmol; Aldrich) in anhydrous dioxane (50 mL) was heated at 90° C. for 72 hours. The reaction mixture was cooled and filtered through a glass frit. The filtrate was concentrated and the residue was purified by silica gel chromatography (50% ethyl acetate in hexane, Rf=0.15) to afford the title compound. MS (APCI) m/z=362 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered through a glass frit
  3. concentrationThe filtrate was concentrated
  4. customthe residue was purified by silica gel chromatography (50% ethyl acetate in hexane, Rf=0.15)

Sources & evidence

ORD record
ord-ecb6eb21277d43a3b11d9f44681e1e4a
Source dataset
uspto-grants-2012_04
Patent number
US08163916B2

Reaction notes

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