Dichloromethane → tert-butyl 4-(6-fluoropyridin-3-yl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 595920Notes

Reaction equation

HRID 595920 reaction equation
[O:1]=[C:2]1[CH:6]=[C:5](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:4][N:3]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(=O)([O-])[O-].[Na+].[Na+].[F:31][C:32]1[N:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C(Cl)Cl>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:31][C:32]1[N:37]=[CH:36][C:35]([C:5]2[CH2:4][N:3]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[C:2](=[O:1])[CH:6]=2)=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 10948184tert-butyl 2-oxo-4-(tosyloxy)-2,5-dihydro-1H-pyrrole-1-carboxylate

Product 1

HCID 118046439tert-butyl 4-(6-fluoropyridin-3-yl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To tert-butyl 2-oxo-4-(tosyloxy)-2,5-dihydro-1H-pyrrole-1-carboxylate (0.8 g, 2.037 mmol) (See Example 24 for synthesis) in DME (27 mL) and sodium carbonate (7 mL, 14.00 mmol) (2M) was added (6-fluoropyridin-3-yl)boronic acid (0.431 g, 3.06 mmol) and PdCl2(dppf).CH2Cl2 adduct (0.333 g, 0.407 mmol). Purge with N2 for 5 min. The reaction mixture was heated in oil bath at 90° C. for 2 h. The reaction mixture was partitioned between ethylacetate and water. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and evaporated. Purified by flash chromatography column using 0-50% EtOAc/heptane. Fractions contains product were combined and evaporated to provide tert-butyl 4-(6-fluoropyridin-3-yl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate as an off white solid (54.7%). LCMS (m/z): 223.2 (MH+-tBu), 0.743 min.

Workup

  1. customPurge with N2 for 5 min
  2. customThe reaction mixture was partitioned between ethylacetate and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customPurified by flash chromatography column
  9. customevaporated

Sources & evidence

ORD record
ord-80f2ed4135254427a18df94e0536d495
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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