Sodium Azide → Methyl (2-chlorophenyl)[4-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1H-1,2,3-triazol-1-yl]acetate

HRID 714712Notes

Reaction equation

HRID 714712 reaction equation
Br[CH:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:13])[C:3]([O:5][CH3:6])=[O:4].[N-:14]=[N+:15]=[N-:16].[Na+].[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]([CH2:34][C@H:35]([OH:40])[C:36]([F:39])([F:38])[F:37])[C:27](=[O:33])[N:28]([CH2:30][C:31]#[CH:32])[N:29]=2)=[CH:21][CH:20]=1>C(#N)C.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[CH:2]([N:14]1[CH:32]=[C:31]([CH2:30][N:28]2[C:27](=[O:33])[N:26]([CH2:34][C@H:35]([OH:40])[C:36]([F:38])([F:37])[F:39])[C:25]([C:22]3[CH:23]=[CH:24][C:19]([Cl:18])=[CH:20][CH:21]=3)=[N:29]2)[N:16]=[N:15]1)[C:3]([O:5][CH3:6])=[O:4]

Participants

6

Reactant 3

HCID 33557Sodium AzideHCID 10730282Methyl alpha-bromo-2-chlorophenylacetateHCID 866909105-(4-Chlorophenyl)-2-(prop-2-yn-1-yl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 69940161Methyl (2-chlorophenyl)[4-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1H-1,2,3-triazol-1-yl]acetate

Reagents, catalysts & solvents 2

HCID 165397Cupric acetate monohydrateCatalystHCID 6342AcetonitrileSolvent

Procedure

361 mg (1.37 mmol) of methyl bromo(2-chlorophenyl)acetate were initially charged in 10 ml of acetonitrile, and 89 mg (1.37 mmol) of sodium azide were added. The mixture was stirred at RT for 1 h. 2.7 mg (0.14 mmol) of copper(II) acetate monohydrate and 569 mg (1.64 mmol) of the compound from Example 14A were then added. The resulting mixture was stirred at 50° C. for 48 h. The reaction mixture was then filtered through a little silica gel, the product being eluted with about 10 ml of ethyl acetate, and the filtrate was concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 8:1→6:1→4:1→2:1→1:1). This gave 496 mg (53% of theory) of the target compound.

Workup

  1. stirringThe resulting mixture was stirred at 50° C. for 48 h
  2. filtrationThe reaction mixture was then filtered through a little silica gel
  3. washthe product being eluted with about 10 ml of ethyl acetate
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe crude product was purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 8:1→6:1→4:1→2:1→1:1)

Sources & evidence

ORD record
ord-5cede3ec2c8948948519de5185247d96
Source dataset
uspto-grants-2015_11
Patent number
US09187466B2

Reaction notes

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