Chloromethyl Methyl Ether → HCID 67058066, compound

HRID 1515097Notes

Reaction equation

HRID 1515097 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]2[N:22]=[CH:21][C:20]([CH:23]([OH:46])[CH2:24][CH2:25][O:26][C:27]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:19][CH:18]=2)[CH:10]=1.[H-].[Na+].[CH3:49][O:50][CH2:51]Cl.[Cl-].[NH4+]>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]([CH:23]([O:46][CH2:49][O:50][CH3:51])[CH2:24][CH2:25][O:26][C:27]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)([C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[CH:21][N:22]=2)[CH:10]=1

Participants

7

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 67058149HCID 67058149, compound

Product 1

HCID 67058066HCID 67058066, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-{6-[(2′,6′-Dimethylbiphenyl-3-yl)methoxy]pyridin-3-yl}-3-(trityloxy)propan-1-ol (250 mg, 0.413 mmol) produced in Example 31 (31C) was dissolved in dimethylformamide (2.5 mL), and sodium hydride (about 63%, oily, 32 mg, 0.83 mmol) was added thereto at 0° C., and then, the resulting mixture was stirred under a nitrogen atmosphere at 0° C. for 50 minutes. Thereafter, chloromethyl methyl ether (0.063 mL, 0.825 mmol) and tetra-n-butyl ammonium iodide (8.0 mg, 0.021 mmol) were sequentially added thereto at 0° C., and the resulting mixture was stirred under a nitrogen atmosphere at 50° C. for 5 hours. To the reaction solution, a saturated aqueous solution of ammonium chloride was added at 0° C., and the organic matter was extracted with ethyl acetate. The organic layer was washed with water, a saturated sodium bicarbonate solution, and a saturated sodium chloride solution, then dried over anhydrous sodium sulfate and filtered. Then, the solvent was distilled off under reduced pressure, whereby a crude product was obtained. This crude product was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 75:25 (v/v)), whereby the objective title compound was obtained (85 mg, yield: 32%).

Workup

  1. stirringat 0° C., and the resulting mixture was stirred under a nitrogen atmosphere at 50° C. for 5 hours
  2. extractionthe organic matter was extracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materiala saturated sodium bicarbonate solution, and a saturated sodium chloride solution, then dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. distillationThen, the solvent was distilled off under reduced pressure, whereby a crude product
  7. customwas obtained
  8. customThis crude product was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 75:25 (v/v)), whereby the objective title compound
  9. customwas obtained (85 mg, yield: 32%)

Sources & evidence

ORD record
ord-632457300a0749238a4bc18f1728a721
Source dataset
uspto-grants-2012_07
Patent number
US08222281B2

Reaction notes

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