Lithium Hydroxide → HCID 86586390, compound

HRID 2417219Notes

Reaction equation

HRID 2417219 reaction equation
[H-].[Na+].[OH:3][CH:4](C)[CH2:5][NH:6][C:7]([C:9]1[O:10][C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[CH:13]=1)=[O:8].C[O:20][C:21](=[O:48])[C:22]1[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([CH3:29])[C:23]=1[N:30]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[S:31]([C:34]1[CH:39]=[CH:38][C:37](F)=[CH:36][CH:35]=1)(=[O:33])=[O:32].[Li+].[OH-]>CN(C=O)C.C1COCC1.O.CO>[O:10]1[C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[CH:13]=[C:9]1[C:7]([NH:6][CH2:5][CH2:4][O:3][C:37]1[CH:38]=[CH:39][C:34]([S:31]([N:30]([C:23]2[C:24]([CH3:29])=[CH:25][C:26]([CH3:28])=[CH:27][C:22]=2[C:21]([OH:48])=[O:20])[CH2:41][C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)(=[O:32])=[O:33])=[CH:35][CH:36]=1)=[O:8]

Participants

9

Reactant 4

HCID 3939Lithium HydroxideHCID 24758Sodium hydrideHCID 15859214HCID 15859214, compoundHCID 43391129HCID 43391129, compound

Product 1

HCID 86586390HCID 86586390, compoundYield 44%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (0.240 g, 5.99 mmol, 60% dispersion in mineral oil) was added to DMF (8 ml) and cooled to 0° C. A solution of N-(2-hydroxypropyl)-1-benzofuran-2-carboxamide (0.6 g, 2.92 mmol) in DMF (1.5 ml) was added and allowed to stir for 10 min at 0° C. and then for 15 min at rt. The product of Example 29 (0.383 g, 0.87 mmol) was then added in one portion and the reaction was allowed to stir overnight. The reaction was then quenched with water, extracted with EtOAc, washed with water, brine, dried over MgSO4, and concentrated in vacuo to provide an oil which was chromatographed using hexane to 2/1 hexane/EtOAc as eluant to provide the product as a mixture of esters which was used directly in the next reaction. The mixture of esters (233 mg) was dissolved in THF:MeOH:H2O (1.2mL:0.7 mL) and LiOH (13.7 mg, 0.32 mmol) was added. The reaction was heated at reflux overnight. The reaction was cooled to rt, quenched with 6M HCl and extracted with CH2Cl2. The organics were washed with brine, dried over Na2SO4, concentrated in vacuo to provide an oil which was chromatographed using hexane to 9/1 CH2Cl2/MeOH as eluant to provide 80 mg (44% yield) of the product acid. Electrospray Mass Spec: m/z 597.2 (M−H)−.

Workup

  1. waitfor 15 min at rt
  2. stirringto stir overnight
  3. customThe reaction was then quenched with water
  4. extractionextracted with EtOAc
  5. washwashed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto provide an oil which
  9. customwas chromatographed
  10. customto provide the product
  11. customwas used directly in the next reaction
  12. temperatureThe reaction was heated
  13. temperatureat reflux overnight
  14. temperatureThe reaction was cooled to rt
  15. customquenched with 6M HCl
  16. extractionextracted with CH2Cl2
  17. washThe organics were washed with brine
  18. dry with materialdried over Na2SO4
  19. concentrationconcentrated in vacuo
  20. customto provide an oil which
  21. customwas chromatographed

Sources & evidence

ORD record
ord-dd8108443a6444ffa15f9684ec707c7f
Source dataset
uspto-grants-2004_11
Patent number
US06825352B2

Reaction notes

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