Sodium hydride → HCID 69593388, compound

HRID 719598Notes

Reaction equation

HRID 719598 reaction equation
[H-].[Na+].[C:3]1([C:9]2[CH:13]=[CH:12][NH:11][CH:10]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:14]([C@@H:18]1[CH2:22][C:21](=[O:23])[O:20][C:19]1=[O:24])[CH:15]([CH3:17])[CH3:16]>O1CCCC1>[CH3:16][CH:15]([CH3:17])[CH2:14][C@H:18]([CH2:22][C:21](=[O:23])[N:11]1[CH:12]=[CH:13][C:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)=[CH:10]1)[C:19]([OH:24])=[O:20].[CH3:16][CH:15]([CH3:17])[CH2:14][C@H:18]([C:19]([N:11]1[CH:12]=[CH:13][C:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)=[CH:10]1)=[O:24])[CH2:22][C:21]([OH:23])=[O:20]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 53241103-phenyl-1H-pyrroleHCID 86593154HCID 86593154, compound

Product 2

HCID 57428095HCID 57428095, compoundHCID 69593388HCID 69593388, compoundYield 5.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (12 mg of 60% dispersion in oil, 0.3 mmol) was added to a stirred solution of 3-phenylpyrrole (43 mg, 0.30 mmol) in tetrahydrofuran (1.0 ml) under nitrogen. The mixture was stirred for 15 minutes then added via cannula to a stirred solution of the (3R)-3-isobutyldihydrofuran-2,5-dione (0.2 mmol) in tetrahydrofuran (1.0 ml) at 0° C., then stirred for 5 hours. The majority of solvents were removed in vacuo then water (10 ml) added. The aqueous layer was extracted with ethyl acetate (5 ml) then saturated aqueous sodium chloride solution (5 ml) added and the aqueous layer extracted with an additional portion of ethyl acetate (5 ml). The aqueous layer was acidified using hydrochloric acid (1M) to pH=1 then the product extracted into ethyl acetate (2×5 ml), dried (MgSO4) and the solvent removed in vacuo. The residue was purified by flash chromatography over silica gel eluting with a gradient of methanol:dichloromethane 1:99→3:17. Appropriate fractions were combined and the solvents removed in vacuo to leave a mixture (approximately 1:1) of (2R)-4-methyl-2-[oxo-2-(3-phenylpyrrol-1-yl)ethyl]pentanoic acid and (3S)-5-Methyl-3-(3-phenyl-pyrrole-1-carbonyl)-hexanoic acid (1.6 mg, 2%) as an oil. TLC (two spots, Rf=0.8 and Rf=0.75, methanol:dichloromethane 1:9), analytical HPLC two unresolved UV peaks with Rt=19.020 and 19.127 mins, HPLC-MS (two unresolved UV peaks with Rt=9.724 and 9.861 mins, 300.2 [M+H]+, 621.3 [2M+Na]+).

Workup

  1. stirringstirred for 5 hours
  2. customThe majority of solvents were removed in vacuo
  3. additionwater (10 ml) added
  4. extractionThe aqueous layer was extracted with ethyl acetate (5 ml)
  5. additionsaturated aqueous sodium chloride solution (5 ml) added
  6. extractionthe aqueous layer extracted with an additional portion of ethyl acetate (5 ml)
  7. extractionthe product extracted into ethyl acetate (2×5 ml)
  8. dry with materialdried (MgSO4)
  9. customthe solvent removed in vacuo
  10. customThe residue was purified by flash chromatography over silica gel eluting with a gradient of methanol:dichloromethane 1:99→3:17
  11. customthe solvents removed in vacuo

Sources & evidence

ORD record
ord-0a1a01f546ba41b889bdf634b71d1a89
Source dataset
uspto-grants-2006_11
Patent number
US07132449B2

Reaction notes

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