Hydrochloric Acid → 1-{9-Chloro-1-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl}-2,2,2-trifluoroethanol

HRID 1629013Notes

Reaction equation

HRID 1629013 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:27]=[O:28])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[C:16]([C:23]([F:26])([F:25])[F:24])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH2:12][CH2:13][CH2:14][N:7]21.[F:29][C:30]([Si](C)(C)C)([F:32])[F:31].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Cl.C(=O)([O-])O.[Na+]>O1CCCC1>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([C:23]([F:24])([F:26])[F:25])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=4)[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:27]([OH:28])[C:30]([F:32])([F:31])[F:29])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 441565019-Chloro-1-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehyde

Product 1

HCID 577862341-{9-Chloro-1-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl}-2,2,2-trifluoroethanolYield 94.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 9-chloro-1-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehyde (336 mg, 0.82 mmol) and (trifluoromethyl)trimethylsilane (0.36 mL, 2.44 mmol) in tetrahydrofuran (10 mL) was added tetrabutylammonium fluoride (1.0M solution in tetrahydrofuran 0.082 mL, 0.082 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 hr. 1N HCl (2.0 mL) was added to the reaction mixture at 0° C. and the mixture was stirred at 0° C. for 0.5 hr. The mixture was basified with aqueous sodium hydrogen carbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture to give the title compound (372.5 mg, 0.775 mmol, 94%) as a pale yellow solid.

Workup

  1. stirringthe mixture was stirred at 0° C. for 0.5 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-d02f550c21cf4704bd1707e10ebb5a35
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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