Sodium Carbonate → methyl 6-(1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)-5-nitronicotinate

HRID 44308

Reaction equation

HRID 44308 reaction equation
Cl[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[C:15]([N:22]1[CH:26]=[CH:25][CH:24]=[C:23]1B(O)O)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:18]([O:17][C:15]([N:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1)=[O:16])([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 346961Methyl 6-chloro-5-nitronicotinateHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic Acid

Product 1

HCID 66926258methyl 6-(1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)-5-nitronicotinateYield 42.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of methyl 6-chloro-5-nitronicotinate (0.108 g, 0.499 mmol), 1-Boc-pyrrole-2-boronic acid (0.210 g, 0.997 mmol), and trans-Dichlorobis(triphenylphosphine)palladium (II) (0.350 g, 0.499 mmol) in Dioxane (Volume: 2.3 mL) was added 2M Sodium carbonate (0.798 mL, 1.596 mmol) at 23° C. The reaction was stirred at 100° C. for 1 hr. The resulting suspension was filtered and rinsed with dioxane and H2O. The filtrate was diluted with EtOAc (20 mL) and the layers were separated. The organic phase was washed with saturated NaHCO3 and brine, dried over MgSO4, filtered, rinsed with EtOAc, and dried in vacuo. The resulting crude material was purified via medium pressure chromatography using a gradient eluant of CH2Cl2/MeOH. The appropriate fractions were combined and concentrated via rotary evaporation to provide methyl 6-(1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)-5-nitronicotinate (0.0738 g, 0.212 mmol, 42.6% yield) as an orange gummy solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.32 (s, 9 H) 3.96 (s, 3 H) 6.41 (t, J=3.28 Hz, 1 H) 6.65 (dd, J=3.28, 1.77 Hz, 1 H) 7.50 (dd, J=3.28, 1.77 Hz, 1 H) 8.82 (d, J=1.77 Hz, 1H) 9.33 (d, J=1.77 Hz, 1 H). ESI-MS: m/z 348.2 (M+H)+.

Workup

  1. filtrationThe resulting suspension was filtered
  2. washrinsed with dioxane and H2O
  3. additionThe filtrate was diluted with EtOAc (20 mL)
  4. customthe layers were separated
  5. washThe organic phase was washed with saturated NaHCO3 and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. washrinsed with EtOAc
  9. customdried in vacuo
  10. customThe resulting crude material was purified via medium pressure chromatography
  11. concentrationconcentrated via rotary evaporation

Sources & evidence

ORD record
ord-5a15741a93b14d449942c6a8e2608357
Source dataset
uspto-grants-2013_09
Patent number
US08541417B2

Linked notes

Loading…