Sodium hydride → HCID 68868661, compound

HRID 1985194Notes

Reaction equation

HRID 1985194 reaction equation
C([O:3][C:4](=[O:32])[C:5]([O:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)([CH3:23])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH:16]2[CH2:20][NH:19][C:18](=[O:21])[N:17]2[CH3:22])=[CH:9][CH:8]=1)C.[H-].[Na+].[CH3:35][C:36]1[CH:37]=[C:38]([CH:41]=[CH:42][C:43]=1[CH3:44])[CH2:39]Cl>CN(C=O)C.CCOCC.Cl>[CH3:35][C:36]1[CH:37]=[C:38]([CH:41]=[CH:42][C:43]=1[CH3:44])[CH2:39][N:19]1[CH2:20][CH:16]([CH2:15][CH2:14][O:13][C:10]2[CH:9]=[CH:8][C:7]([CH2:6][C:5]([O:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)([CH3:23])[C:4]([OH:3])=[O:32])=[CH:12][CH:11]=2)[N:17]([CH3:22])[C:18]1=[O:21]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 660183,4-Dimethylbenzyl chlorideHCID 68868398HCID 68868398, compound

Product 1

HCID 68868661HCID 68868661, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 80 mg of 2-(4-Fluoro-phenoxy)-2-methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-propionic acid ethyl ester in 5 mL of dry DMF at 0° C. under an atmosphere of nitrogen, 18 mg of NaH (0.45 mmol) is added. The resulting solution is allowed to stand at r.t. for 20 min. Then 0.07 mL of 3,4-dimethylbenzyl chloride is added and resulting mixture is allowed to stand at r.t. for overnight. Reaction mixture is diluted with Et2O and 1N HCl. Organic layer is then washed with 1N HCl (2×10 mL), brine (2×10 mL), dried over Na2SO4, filtered and concentrated under vacuum. The crude material is in 5 mL of EtOH and 0.4 mL of 5N NaOH. The mixture is heated to reflux for 1 h. The organic solvent is then removed under vacuum and residue is dissolved in CH2Cl2 and 1N HCl. Aqueous layer is washed with CH2Cl2 (2×10 mL). Combined organic layer is dried over Na2SO4, filtered and concentrated under vacuum. The crude material is purified by MS/LC to give 54 mg (56%) of the title product. 1H NMR (400 MHz, CDCl3): δ 7.18 (d, 2H, J=8.4 Hz), 7.06 (d, 1H, J=7.6 Hz), 7.00 (s, 1H), 6.97-6.85 (m, 5H), 6.75 (d, 2H, J=8.4 Hz), 4.34, 4.25 (ABq, 2H, J=15.0 Hz), 4.31 (bs, 1H), 3.98-3.90 (m, 2H), 3.69-3.61 (m, 1H), 3.39 (t, 1H, J=8.7 Hz), 3.25, 3.11 (ABq, 2H, J=14.0 Hz), 3.00 (t, 1H, J=8.7 Hz), 2.84 (s, 3H), 2.29-2.17 (m, 1H), 2.22 (s, 6H), 1.94-1.87 (m, 1H), 1.37 (s, 3H). HRMS (ES+) m/z exact mass calcd for C31H36N2O5F (m+1) 535.2608, found 535.2614.

Workup

  1. customresulting mixture
  2. waitto stand at r.t. for overnight
  3. customReaction mixture
  4. washOrganic layer is then washed with 1N HCl (2×10 mL), brine (2×10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. temperatureThe mixture is heated
  9. temperatureto reflux for 1 h
  10. customThe organic solvent is then removed under vacuum and residue
  11. dissolutionis dissolved in CH2Cl2
  12. washAqueous layer is washed with CH2Cl2 (2×10 mL)
  13. dry with materialCombined organic layer is dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated under vacuum
  16. customThe crude material is purified by MS/LC

Sources & evidence

ORD record
ord-c16b9bd3afd445be9935f0f96b2e007b
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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