Potassium Carbonate → HCID 69003760, compound

HRID 750062Notes

Reaction equation

HRID 750062 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]2[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:32]3[CH:33]=[CH:34][N:29]=[CH:30][CH:31]=3)=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 2734379(Pyridin-4-yl)boronic acidHCID 68996388HCID 68996388, compound

Product 1

HCID 69003760HCID 69003760, compoundYield 60%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a 20 mL press resistant vial which contained a suspension of (R)-2-[4-(4-iodo-benzyl)phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 0.4 mmol), pyridine-4-boronic acid (110 mg, 0.8 mmol), palladium(II) acetate (10 mg, 0.05 mmol) and triphenyl phosphine (30 mg, 0.1 mmol) in DME (5 mL) was added potassium carbonate (100 mg, 0.7 mmol), ethanol (0.05 mL) and water (0.05 mL) at rt. The tube was sealed and the mixture was allowed to warm to rt and stir at rt for 30 min and then was heated to 98° C. and stirred at 98° C. for 16 h. After cooled to rt, the mixture was poured onto 200 mL ice-water solution and then extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (2×30 mL) and brine (20 mL). and dried over anhy. Na2SO4. The solvent was removed in vacuo to obtain the crude product which was purified by silica gel flash chromatography to afford the title product (100 mg, 60%); 1H NMR (400 MHz, CDCl3); δ 1.47 (s, 9H), 1.79-2.08 (m, 4H), 3.27-3.44 (m, 2H), 3.70-3.96 (m, 1H), 3.97 (s, 2H), 4.04-4.20 (m, 2H), 6.82-6.86 (m, 2H), 7.11 (d, J=8.8 Hz, 2H), 7.29 (d, J=8.4 Hz, 2H), 7.48 (d, J=6.0 Hz, 2H), 7.56 (d, J=8.4 Hz, 2H), 8.63 (d, J=6.0 Hz, 2H):

Workup

  1. customThe tube was sealed
  2. temperaturewas heated to 98° C.
  3. stirringstirred at 98° C. for 16 h
  4. temperatureAfter cooled to rt
  5. extractionextracted with EtOAc (3×30 mL)
  6. washThe combined organic layers were washed with water (2×30 mL) and brine (20 mL)
  7. customand dried over anhy
  8. customThe solvent was removed in vacuo
  9. customto obtain the crude product which
  10. customwas purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-8b904fee486a4c8da35f439be4bd8b18
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Reaction notes

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