Potassium Carbonate → HCID 68998064, compound

HRID 1909656Notes

Reaction equation

HRID 1909656 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:19]=[CH:18][C:10]([O:11][CH2:12][C@@H:13]3[CH2:17][CH2:16][CH2:15][NH:14]3)=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.Br[CH2:23][CH2:24][CH2:25][N:26]1[C:30](=[O:31])[C:29]2=[CH:32][CH:33]=[CH:34][CH:35]=[C:28]2[C:27]1=[O:36].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:19]=[CH:18][C:10]([O:11][CH2:12][C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[CH2:23][CH2:24][CH2:25][N:26]3[C:30](=[O:31])[C:29]4[C:28](=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:27]3=[O:36])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 21611N-3-BromopropylphthalimideHCID 44819170HCID 44819170, compound

Product 1

HCID 68998064HCID 68998064, compoundYield 61,246.199%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

(S)-2-[4-(4-Chloro-phenoxy)-phenoxymethyl]-pyrrolidine (200 mg, 0.658 mmol) was taken into anhydrous DMF (2 mL) in a nitrogen flushed 20 mL vial. N-(3-Bromopropyl)phthalimide (194 mg, 0.724 mmol) was added to the mixture followed by potassium carbonate (364 mg, 2.43 mmol). The reaction was sealed and heated at 60° C. for 24 h. The mixture was then cooled to room temperature and partitioned between ethyl acetate and water. The water layer was washed with ethyl acetate (3×). The combined ethyl acetate layers were then washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness. The resulting residue was then purified by silica gel flash chromatography (20:1 silica ratio, eluted with 40% methanol in dichloromethane). The overlap from the purification was repurified by silica gel flash chromatography (20:1 silica ratio, eluted with 1% methanol in dichloromethane followed by 5% methanol in dichloromethane) to obtain the title product (198 mg, 403 mmol, 61%); MS; m/z 491 (M); 1H NMR (400 MHz, DMSO-d6) δ 1.5-1.67 (m, 3H), 1.75-1.82 (m, 2H), 1.86-1.91 (m, 1H), 2.13-2.14 (m, 1H), 2.34-2.37 (m, 1H), 2.72-2.73 (m, 1H), 2.89-2.94 (m, 1H), 3.02-3.06 (m, 1H), 3.60-3.70 (m, 3H), 3.88-3.91 (m, 1H), 6.89-6.98 (m, 6H), 7.38 (d, J=9.2, 2H), 7.82-7.85 (m, 4H).

Workup

  1. customflushed 20 mL vial
  2. customThe reaction was sealed
  3. temperatureThe mixture was then cooled to room temperature
  4. custompartitioned between ethyl acetate and water
  5. washThe water layer was washed with ethyl acetate (3×)
  6. washThe combined ethyl acetate layers were then washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe resulting residue was then purified by silica gel flash chromatography (20:1 silica ratio, eluted with 40% methanol in dichloromethane)
  11. customThe overlap from the purification
  12. customwas repurified by silica gel flash chromatography (20:1 silica ratio, eluted with 1% methanol in dichloromethane followed by 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-e282af07c40f41149ae1c331d82cc631
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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