Acetonitrile → HCID 178485426, compound

HRID 448951Notes

Reaction equation

HRID 448951 reaction equation
[CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH2:10][CH2:11][C:12]1[NH:16][N:15]=[N:14][N:13]=1.C([O-])(O)=O.[Na+].[Cl:22][C:23]1[C:31]([C:32]2[CH:33]=[N:34][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:36][CH:37]=2)=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1.[C:42](#[N:44])C>>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([C:27]([N:2]([CH3:1])[C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[O:9][CH2:10][CH2:11][C:12]2[NH:16][N:15]=[N:14][N:13]=2)=[O:28])=[CH:30][C:31]=1[C:32]1[CH:33]=[N:34][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:36][C:37]=1[C:42]#[N:44]

Participants

5

Reactant 4

HCID 6342Acetonitrile2×HCID 516892Sodium BicarbonateHCID 866425814-Chloro-5-(6-trifluoromethyl-pyridin-3-yl)-benzoyl chlorideHCID 178482136Methyl-{2-[2-(1H-tetrazol-5-yl)-ethoxy]-phenyl}-amine

Product 1

HCID 178485426HCID 178485426, compound

Procedure

The stirring aqueous solution of methyl-{2-[2-(1H-tetrazol-5-yl)-ethoxy]-phenyl}-amine was basified with sat. NaHCO3 and diluted with acetonitrile (40 mL). 4-Chloro-5-(6-trifluoromethyl-pyridin-3-yl)-benzoyl chloride (Step 39A, 2.9 g, 8.8 mmol) in acetonitrile (20 mL) was added dropwise. The mixture was stirred for 2 hrs, acidified, and concentrated to remove acetonitrile. The concentrated mixture was extracted with ethyl acetate. The organic layer was then washed with water and brine, and was dried over MgSO4. After filtration and concentration, the residue was purified via silica gel flash column chromatography eluting with 2% MeOH in DCM and then further purified via silica gel flash column chromatography eluting with 50% ethyl acetate in hexane to produce 4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-N-methyl-N-{2-[2-(1H-tetrazol-5-yl)-ethoxy]-phenyl}-benzamide 45-1 (3.2 g). [M+H]+528.2; tR=3.43 min (method 3).

Workup

  1. concentrationconcentrated
  2. customto remove acetonitrile
  3. extractionThe concentrated mixture was extracted with ethyl acetate
  4. washThe organic layer was then washed with water and brine
  5. dry with materialwas dried over MgSO4
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified via silica gel flash column chromatography
  8. washeluting with 2% MeOH in DCM
  9. customfurther purified via silica gel flash column chromatography
  10. washeluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-4b8e0a2af7344bd881743c3bd11978bc
Source dataset
uspto-grants-2013_07
Patent number
US08481738B2

Reaction notes

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