Sodium Hydroxide → 2-(2,3-Difluorophenyl)-5-[[4-(trifluoromethoxy)phenyl]methyl]-5H-imidazo[4,5-c]pyridine

HRID 1992532Notes

Reaction equation

HRID 1992532 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[NH:17][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][C:11]=2[N:10]=1.[OH-].[Na+].Cl[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=1>CN(C=O)C>[F:30][C:29]([F:31])([F:32])[O:28][C:25]1[CH:26]=[CH:27][C:22]([CH2:21][N:14]2[CH:15]=[CH:16][C:11]3=[N:10][C:9]([C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=4[F:1])=[N:17][C:12]3=[CH:13]2)=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 27772614-(Trifluoromethoxy)benzyl ChlorideHCID 272821652-(2,3-Difluorophenyl)-3H-imidazo[4,5-c]pyridine2×

Product 1

HCID 444271672-(2,3-Difluorophenyl)-5-[[4-(trifluoromethoxy)phenyl]methyl]-5H-imidazo[4,5-c]pyridineYield 1,116.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

First, 2-(2,3-difluorophenyl)-3H-imidazo[4,5-c]pyridine (20 g, 86.6 mmole) was added to 430 mL of DMF. Some of the solid material did not dissolve. To this solution was added 43 mL of a 10% NaOH (w/v) solution. With vigorous stirring, the un-dissolved material went into solution. The resulting solution was divided into 30 equal portions of 16.3 mL, 3 mmole of 2-(2,3-difluorophenyl)-3H-imidazo[4,5-c]pyridine so as to fit into a microwave reaction vessel. To each reaction vessel was added of 1-(chloromethyl)-4-(trifluoromethoxy)benzene (693 mg, 3 mmole). Each reaction mixture was microwaved for 1 minute at 110° C. Following the completion of all the microwave reactions, all of the reaction vessels were combined (one was lost due to breakage of the vessel) into three batches for workup. For each batch, DMF was removed by vacuum, and the resulting material washed three times with deionized water. The resulting crude material was dissolved in CH2Cl2, Purified using a 330 g SiO2 column (Redisep (Isco) 0% to 0%/5 min to 10% B/30 min to 20%/5 min), and the resulting material was re-crystallized from ethanol/H2O. The three batches yielded 14 g, 33.5 mmole of 5-(4-(trifluoromethoxy)benzyl)-2-(2,3-difluorophenyl)-5H-imidazo[4,5-c]pyridine. 1H 300 Mhz (CD3OD) sigma 5.79 (s, 2p); 7.25-7.35 (m, 1p); 7.37 (d, 2p); 7.38-7.42 (m, 2p); 7.55 (d, 2p); 7.88-7.95 (m, 1p); 8.25 (d, 1p); and 9.05 (s, 1p). LC/MS M/z=406.23.

Workup

  1. dissolutionSome of the solid material did not dissolve
  2. customto fit into a microwave reaction vessel
  3. customEach reaction mixture was microwaved for 1 minute at 110° C
  4. customall of the reaction vessels
  5. customFor each batch, DMF was removed by vacuum
  6. washthe resulting material washed three times with deionized water
  7. dissolutionThe resulting crude material was dissolved in CH2Cl2
  8. customPurified
  9. customa 330 g SiO2 column (Redisep (Isco) 0% to 0%/5 min to 10% B/30 min to 20%/5 min)
  10. customthe resulting material was re-crystallized from ethanol/H2O

Sources & evidence

ORD record
ord-41eb1463a1f14e3fac9a27f7ac5680c2
Source dataset
uspto-grants-2010_01
Patent number
US07648998B2

Reaction notes

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