Potassium Carbonate → HCID 86611563, compound

HRID 1909745Notes

Reaction equation

HRID 1909745 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].[S:29]1[CH:33]=[CH:32][CH:31]=[C:30]1B(O)O.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[C:27]([C:30]3[S:29][CH:33]=[CH:32][CH:31]=3)=[CH:26][CH:25]=[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 27339602-Thiopheneboronic acidHCID 68996388HCID 68996388, compound

Product 1

HCID 86611563HCID 86611563, compoundYield 75.6%

Reagents, catalysts & solvents 4

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

Procedure

To a 20 mL pressure resistant vial which contained a suspension of (R)-2-[4-(4-iodo-benzyl)phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (100 mg, 0.2 mmol), thiophene-2-boronic acid (52 mg, 0.4 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 cooling 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 desired product (68 mg, 75% yield); LCMS; 100%, APCI+, Calcd: 449.6; Found m/z: 449.6, M); 1H NMR (400 MHz, CDCl3); δ 1.46 (s, 9H), 1.79-2.08 (m, 4H), 3.27-3.44 (m, 2H), 3.70-3.95 (m, 1H), 3.92 (s, 2H), 4.03-4.18 (m, 2H), 6.91 (d, J=8.0 Hz, 2H), 7.09-7.11 (m, 1H), 7.16 (d, J=8.8 Hz, 2H), 7.26 (d, J=8.4 Hz, 2H), 7.39-7.42 (m, 2H), 7.58 (d, J=8.4 Hz, 2H):

Workup

  1. customThe tube was sealed
  2. temperaturewas heated to 98° C.
  3. stirringstirred at 98° C. for 16 h
  4. temperatureAfter cooling 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. customdried 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-33ea52e0406a4e07859aa2d343416ce3
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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