Ammonium Chloride → (-)-2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetamide

HRID 417161Notes

Reaction equation

HRID 417161 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:14](O)=[O:15])[C:11]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[Cl-].[NH4+].C([N:33](C(C)C)C(C)C)C.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]3)[C:14]([NH2:33])=[O:15])[C:11]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=3[N:9]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66619321[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid

Product 1

HCID 66619362(-)-2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a turbid solution of 1 g (2.47 mMol) (−)-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid in 15 ml N,N-dimethyl formamide were added 0.264 g (4.94 mmol) ammonium chloride, 0.42 ml (2.47 mmol) ethyl diisopropylamine, 0.378 g (2.47 mmol) N-hydroxybenzotriazole monohydrate and 0.947 g (4.94 mmol) N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride. The reaction mixture is stirred for 14 h at room temperature and then poured onto water. The phases were separated and the aqueous phase extracted three times with ethyl acetate. The combined organic layers were twice washed with water, once with brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by silica gel column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with ethyl acetate. Colorless solid (93%). MS (Turbo Spray): m/z=404.3 [M+H].

Workup

  1. additionpoured onto water
  2. customThe phases were separated
  3. extractionthe aqueous phase extracted three times with ethyl acetate
  4. washThe combined organic layers were twice washed with water, once with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-3c861410a5a94fdb890801047dcd507d
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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