Ammonium Acetate → HCID 178442426, compound

HRID 1881499Notes

Reaction equation

HRID 1881499 reaction equation
C([O-])(=O)C.[NH4+:5].[CH3:6][C:7]([CH3:45])([CH2:43][CH3:44])[CH2:8][C:9](=O)[CH2:10][NH:11][C:12]([C:14]1([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=3)=[CH:31][CH:30]=2)[CH2:18][C:17]([F:20])([F:19])[CH2:16][N:15]1C(OC(C)(C)C)=O)=O>C(OCC)(=O)C.O>[CH3:45][C:7]([CH3:6])([CH2:43][CH3:44])[CH2:8][C:9]1[N:5]=[C:12]([C:14]2([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=4)=[CH:31][CH:30]=3)[CH2:18][C:17]([F:20])([F:19])[CH2:16][NH:15]2)[NH:11][CH:10]=1

Participants

5

Reactant 2

HCID 517165Ammonium AcetateHCID 66705635Tert-butyl 2-{[(4,4-dimethyl-2-oxohexyl)amino]carbonyl}-4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]pyrrolidine-1-carboxylate

Product 1

HCID 178442426HCID 178442426, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

Ammonium acetate (947 mg, 12.3 mmol) was added to an ambient temperature solution of tert-butyl 2-{[(4,4-dimethyl-2-oxohexyl)amino]carbonyl}-4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]pyrrolidine-1-carboxylate (138 mg, 0.25 mmol) in xylenes (10 mL). After stirring in a sealed tube at 160° C. for 1 h, the reaction mixture was diluted with ethyl acetate and water. The organic phase was dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue was purified by chromatography over silica eluting with 0-100% ethyl acetate/hexane followed by high pressure liquid chromatography (KR100-5C18 100×21.2 mm column) eluting with 10-100% acetonitrile/water containing 0.05% trifluoroacetic acid. The residue was dissolved in trifluoroacetic acid (1 mL). After stirring at ambient temperature for 2 h, the reaction mixture was concentrated to afford the title compound. (M+H) found: 443.

Workup

  1. dry with materialThe organic phase was dried (magnesium sulfate)
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by chromatography over silica eluting with 0-100% ethyl acetate/hexane
  5. washeluting with 10-100% acetonitrile/water containing 0.05% trifluoroacetic acid
  6. dissolutionThe residue was dissolved in trifluoroacetic acid (1 mL)
  7. stirringAfter stirring at ambient temperature for 2 h
  8. concentrationthe reaction mixture was concentrated

Sources & evidence

ORD record
ord-d33fcb74c5b843cd9f095a222ca92d91
Source dataset
uspto-grants-2012_11
Patent number
US08318767B2

Reaction notes

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