Water → HCID 59560532, compound

HRID 1176182Notes

Reaction equation

HRID 1176182 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH2:10][C@@:9]3([CH2:15][N:14]4[CH2:16][CH2:17][CH:11]3[CH2:12][CH2:13]4)[O:8][C:5]2=[N:6][CH:7]=1.O.[CH:19]([C:21]1[O:25][C:24](B(O)O)=[CH:23][CH:22]=1)=[O:20].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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.CCO>[O:8]1[C:5]2=[N:6][CH:7]=[C:2]([C:24]3[O:25][C:21]([CH:19]=[O:20])=[CH:22][CH:23]=3)[CH:3]=[C:4]2[CH2:10][C@:9]21[CH2:15][N:14]1[CH2:16][CH2:17][CH:11]2[CH2:12][CH2:13]1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343555-Formylfuran-2-boronic acidHCID 54506690(2R)-5'-bromo-3'H-spiro[4-azabicyclo[2.2.2]octane-2,2'-furo[2,3-b]pyridine]

Product 1

HCID 59560532HCID 59560532, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of (2R)-5′-bromo-3′H-spiro[4-azabicyclo[2.2.2]octane-2,2′-furo[2,3-b]pyridine] (6 g, 20.3 mmol) in 400 mL of a DME:H2O:EtOH mixture (7:3:2) was added 5-formyl-2-furanboronic acid (5.67 g, 40.5 mmol). The reaction mixture was purged with N2 (directly into the solvent) and stirred for ten minutes until homogeneous. Solid Na2CO3 (8.6 g, 81.0 mmol) was added to the reaction mixture followed by Pd(PPh3)2Cl2 (711 mg, 1.0 mmol). The reaction mixture was again purged with N2 for 10 min, then heated at 65° C. for 6 h. The reaction mixture was stirred at rt overnight, then concentrated via rotary evaporator. The resulting residue was diluted with CHCl3 and filtered through diatomaceous earth. The CHCl3 filtrate was concentrated and the resulting residue was diluted with 1N HCl and extracted with EtOAc (3×150 mL). The acidic aqueous layer was made basic with the addition of 2N aqueous NaOH (to pH˜12) and the basic aqueous solution was extracted with CHCl3 (3×150 mL). The combined CHCl3 layer was washed with brine, dried (Na2SO4), filtered and concentrated to a solid (5.79 g, 92% yield). This material was used without further purification. 1H NMR (500 MHz, CDCl3) δ 1.46-1.53 (m, 1H), 1.68-1.71 (m, 2H), 2.03-2.04 (m, 1H), 2.22-2.26 (m, 1H), 2.78-2.94 (m, 3H), 2.97 (d, J=14.7 Hz, 1H), 3.00-3.04 (m, 1H), 3.07 (d, J=16.5 Hz, 1H), 3.40 (d, J=14.7 Hz, 1H), 3.47 (d, J=16.5 Hz, 1H), 6.74 (d, J=3.7 Hz, 1H), 7.30 (d, J=3.7 Hz, 1H), 7.89 (s, 1H), 8.48 (s, 1H), 9.62 (s, 1H) MS ES+, m/z=311 (M+H+).

Workup

  1. customThe reaction mixture was purged with N2 (directly into the solvent) and
  2. customThe reaction mixture was again purged with N2 for 10 min
  3. stirringThe reaction mixture was stirred at rt overnight
  4. concentrationconcentrated via rotary evaporator
  5. additionThe resulting residue was diluted with CHCl3
  6. filtrationfiltered through diatomaceous earth
  7. concentrationThe CHCl3 filtrate was concentrated
  8. additionthe resulting residue was diluted with 1N HCl
  9. extractionextracted with EtOAc (3×150 mL)
  10. additionThe acidic aqueous layer was made basic with the addition of 2N aqueous NaOH (to pH˜12)
  11. extractionthe basic aqueous solution was extracted with CHCl3 (3×150 mL)
  12. washThe combined CHCl3 layer was washed with brine
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered

Sources & evidence

ORD record
ord-9e8bc0270bf14928925511b352ff99f1
Source dataset
uspto-grants-2010_11
Patent number
US07842803B2

Reaction notes

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