Sodium hydride → HCID 178522846, compound

HRID 1023871Notes

Reaction equation

HRID 1023871 reaction equation
C([N:20]1[CH:24]=[C:23]([C:25]2[CH:42]=[CH:41][CH:40]=[CH:39][C:26]=2[O:27][CH2:28][CH:29]=[C:30]2[CH2:35][CH2:34][CH:33]([C:36]([NH2:38])=[O:37])[CH2:32][CH2:31]2)[N:22]=[CH:21]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+].[Cl:45][C:46]1[CH:47]=[C:48]([CH:51]=[CH:52][CH:53]=1)[CH2:49]Br>CN(C=O)C.O>[NH:20]1[CH:24]=[C:23]([C:25]2[CH:42]=[CH:41][CH:40]=[CH:39][C:26]=2[O:27][CH2:28][CH:29]=[C:30]2[CH2:35][CH2:34][CH:33]([C:36]([NH:38][CH2:49][C:48]3[CH:51]=[CH:52][CH:53]=[C:46]([Cl:45])[CH:47]=3)=[O:37])[CH2:32][CH2:31]2)[N:22]=[CH:21]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 698381-(Bromomethyl)-3-chlorobenzeneHCID 67207767HCID 67207767, compound

Product 1

HCID 178522846HCID 178522846, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-(2-(2-(1-trityl-1H-imidazol-4-yl)phenoxy)ethylidene)cyclohexanecarboxamide (177 mg, 0.320 mmol) in anhydrous DMF (3 mL) at 0° C. was added NaH (9.0 mg, 0.384 mmol). The resulting suspension was allowed to stir at room temperature for 45 min. To the resulting solution was added 3-chlorobenzyl bromide (79 mg, 0.384 mmol). After stirring overnight, the reaction mixture was carefully diluted with water and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with water, brine and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product was taken to next step without further purification. To a solution of the crude ether was added acetic acid (1.0 mL) and MeOH (4.0 mL). The solution was stirred at 80° C. for 2 h. The solution was allowed to cool to room temperature and the pH was adjusted to ˜10 with 10% NaOH (aq). The aqueous phase was extracted with EtOAc (3×20 mL). The combined organic layer were washed with water, brine, and dried. The solvent was removed in vacuo to afford the crude residue, which was purified by flash column chromatography on silica gel to afford the desired product (47 mg, 0.108 mmol, 34%). 1H NMR (DMSO-d6): 1.44-1.52 (m, 4H), 1.69-1.79 (m, 4H), 2.19-2.23 (m, 1H), 3.85 (s, 2H), 4.05-4.11 (m, 2H), 6.63 (d, 1H, J=10.5 Hz), 6.88-6.93 (m, 2H), 6.99 (t, 1H, J=6.8 Hz), 7.09-7.11 (m, 2H), 7.18 (d, 1H, J=7.6 Hz), 7.25 (t, 1H, J=7.6 Hz), 7.41-7.48 (m, 2H), 7.65 (s, 1H), 7.93 (s, 1H).

Workup

  1. stirringAfter stirring overnight
  2. extractionextracted with ethyl acetate (2×10 mL)
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried (Na2SO4)
  5. customThe solvent was removed under reduced pressure
  6. customthe crude product was taken to next step without further purification
  7. additionTo a solution of the crude ether was added acetic acid (1.0 mL) and MeOH (4.0 mL)
  8. stirringThe solution was stirred at 80° C. for 2 h
  9. temperatureto cool to room temperature
  10. extractionThe aqueous phase was extracted with EtOAc (3×20 mL)
  11. washThe combined organic layer were washed with water, brine
  12. customdried
  13. customThe solvent was removed in vacuo
  14. customto afford the crude residue, which
  15. customwas purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-c1f75c3613f9422a9eaa732e21484a02
Source dataset
uspto-grants-2014_05
Patent number
US08722720B2

Reaction notes

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