Cesium fluoride → HCID 66611623, compound

HRID 1812330Notes

Reaction equation

HRID 1812330 reaction equation
[CH3:1][O:2][C:3]1[CH:35]=[CH:34][C:6]([CH2:7][N:8]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([F:24])=[N:18][CH:19]=[C:20]([CH:23]=3)[CH:21]=[O:22])[N:10]=2)=[CH:5][CH:4]=1.C[Si](C)(C)[C:38]([F:41])([F:40])[F:39].[F-].[Cs+]>C1COCC1>[CH3:33][O:32][C:29]1[CH:28]=[CH:27][C:26]([CH2:25][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:35][CH:34]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:23]=[C:20]([CH:21]([OH:22])[C:38]([F:41])([F:40])[F:39])[CH:19]=[N:18][C:17]=3[F:24])[N:10]=2)=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 86647074HCID 86647074, compound

Product 1

HCID 66611623HCID 66611623, compoundYield 108%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoronicotinaldehyde (3.7810 g, 7.99 mmol; Example 143, Step 1-2) in THF (50.00 mL) was added trimethyl(trifluoromethyl)silane (TCI America, Inc.; 1.703 g, 11.98 mmol) followed by CsF (0.243 g, 1.597 mmol) at 0° C. and the mixture was stirred at the same temperature for 10 min before warming to room temperature and stirring for 3.5 h. The reaction was quenched with 1 N HCl and stirred for another 30 min, and then EtOAc (10 mL) was added. The separated aqueous layer was extracted with ethyl acetate (2×20 mL) and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give a brown foam residue as the desired product 1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)-2,2,2-trifluoroethanol (4.69 g, 8.63 mmol, 108% yield) which was used directly for the next step.

Workup

  1. stirringstirring for 3.5 h
  2. customThe reaction was quenched with 1 N HCl
  3. stirringstirred for another 30 min
  4. additionEtOAc (10 mL) was added
  5. extractionThe separated aqueous layer was extracted with ethyl acetate (2×20 mL)
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4c61a3dd291a472499a348ef75b6080f
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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