2,5-Dibromopyridine → HCID 66846469, compound

HRID 253186Notes

Reaction equation

HRID 253186 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][NH:12][CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][N:18]=1.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.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]2[CH:14]([CH2:13][N:12]([C:17]3[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][N:18]=3)[CH2:11]2)[CH2:15]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 693532,5-DibromopyridineHCID 634876Binap, (A+-)-HCID 4142526Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 66846469HCID 66846469, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid tert-butyl ester (7.0317 g, 33.2 mmol) in 180 mL toluene was added 2,5-dibromopyridine (22.03 g, 92.9 mmol), tris(dibenzylidenacetone)dipalladium (0) (Pd2(dba)3, Strem, 0.6087 g, 0.664 mmol), 2,2′-bis(diphenyphosphino)-1,1′binaphthyl (BINAP, Aldrich, 1.0506 g, 1.68 mmol), and NaOtBu (Aldrich, 4.778 g, 49.7 mmol. The reaction mixture was heated to 90° C. under dry N2 for 6 hours. The reaction mixture was cooled to room temperature and was filtered through diatomaceous earth and the residue was washed with 250 mL ethyl acetate. The combined organic extracts were concentrated under reduced pressure. The residue was purified via column chromatography (SiO2, gradient 5% to 60% EtOAc-hexanes) to give 7.71 g (20.6 mmol, 62% yield). H NMR (300 MHz) δ 1.45 (s, 9H) 2.94-3.14 (m, 2H) 3.17-3.38 (m, 4H) 3.51-3.76 (m, 4H) 6.46 (d, J=9 Hz, 1H) 7.59 (dd, J=9, 3 Hz, 1H) 8.05 ppm (s, 1H)

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationwas filtered through diatomaceous earth
  3. washthe residue was washed with 250 mL ethyl acetate
  4. concentrationThe combined organic extracts were concentrated under reduced pressure
  5. customThe residue was purified via column chromatography (SiO2, gradient 5% to 60% EtOAc-hexanes)
  6. customto give 7.71 g (20.6 mmol, 62% yield)

Sources & evidence

ORD record
ord-b7e33b3bc7034c9690df614178f81ca0
Source dataset
uspto-grants-2011_01
Patent number
US07872010B2

Reaction notes

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