Phenylhydrazine → HCID 46893525, compound

HRID 1879625Notes

Reaction equation

HRID 1879625 reaction equation
[Cl:1][C:2]1[C:3](F)=[C:4]([C:12](=O)[CH:13]([CH:21]([C:25]2[CH:42]=[CH:41][C:28]([C:29]([NH:31][CH2:32][CH2:33][C:34]([O:36]C(C)(C)C)=[O:35])=[O:30])=[CH:27][CH:26]=2)[CH2:22][CH2:23][CH3:24])[C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[C:45]1([NH:51][NH2:52])[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>N1C=CC=CC=1.CCOC(C)=O>[Cl:20][C:17]1[CH:16]=[CH:15][C:14]([CH:13]([C:12]2[N:51]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[N:52]=[C:3]3[C:4]=2[CH:5]=[C:6]([C:8]([F:10])([F:9])[F:11])[CH:7]=[C:2]3[Cl:1])[CH:21]([C:25]2[CH:42]=[CH:41][C:28]([C:29]([NH:31][CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[O:30])=[CH:27][CH:26]=2)[CH2:22][CH2:23][CH3:24])=[CH:19][CH:18]=1

Participants

5

Reactant 2

HCID 7516PhenylhydrazineHCID 58538065HCID 58538065, compound

Product 1

HCID 46893525HCID 46893525, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of the major diastereomer of tert-butyl N-(4-{1-[2-[3-chloro-2-fluoro-5-(trifluoromethyl)phenyl]-1-(4-chlorophenyl)-2-oxoethyl]butyl}benzoyl)-β-alaninate (EXAMPLE 2, Step A, 100 mg, 0.153 mmol) in pyridine (1.5 mL) was added phenylhydrazine (0.083 mL, 0.076 mmol). The mixture was stirred at 80° C. for 18 hours in a sealed tube. The mixture was diluted with EtOAc then washed with 2 N HCl (aq) then saturated NaCl (aq). The organic layer was dried over sodium sulfate, filtered, then concentrated. The resulting residue was purified by silica gel chromatography eluting with 0-50% EtOAc/hexanes to afford the title compound. This diastereomer was resolved to provide enantiopure material by HPLC on a ChiralPak IA column (2 cm×25 cm) eluting with 9 mL/min of 5% EtOH/n-heptane. LC1 2.98 min. (M-tBu+H)+ 668.

Workup

  1. washthen washed with 2 N HCl (aq)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified by silica gel chromatography
  6. washeluting with 0-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-d829785465034dde9381cfc7d831b2f4
Source dataset
uspto-grants-2012_11
Patent number
US08318667B2

Reaction notes

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