Tetrahydrofuran → HCID 58011702, compound

HRID 660959Notes

Reaction equation

HRID 660959 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][CH:14]=[O:15])[C:11](=[O:16])[N:10]([CH2:17][C:18]([NH:20][CH:21]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)[CH2:22]C)=[O:19])[N:9]=2)=[CH:4][CH:3]=1.[CH2:34]1COC[CH2:35]1.[CH2:39]([Mg]Br)C>C(OCC)C.[Ti+4]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([CH2:13][C:14]3([OH:15])[CH2:35][CH2:34]3)[C:11](=[O:16])[N:10]([CH2:17][C:18]([NH:20][C:21]([CH3:39])([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:32])([F:31])[F:33])[CH:25]=3)[CH3:22])=[O:19])[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 86637210HCID 86637210, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 58011702HCID 58011702, compound

Reagents, catalysts & solvents 2

HCID 114942Titanium cation (4+)CatalystHCID 3283Diethyl EtherSolvent2×

Procedure

72 mg (0.14 mmol) of 2-[3-(4-chlorophenyl)-4-(2-oxoethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-{-methyl-1-[3-(trifluoromethyl)phenyl]ethyl}-acetamide from Example 401 together with 4 mg (0.014 mmol) of titanium(IV) isopropylate are dissolved in 0.45 ml of diethyl ether and 0.3 ml of THF and treated at RT within 1 hr with 108 μl (0.32 mmol) of ethylmagnesium bromide (3 M solution in diethyl ether), diluted with 0.4 ml diethyl ether. This is stirred for a further 10 mins at RT. For the workup, the mixture is poured into 10 ml of ice-cold 10% sulphuric acid and extracted twice with 10 ml of ethyl acetate each time. The combined organic phases are dried over sodium sulphate, filtered and concentrated in vacuo. The crude product is purified by preparative HPLC [Method 10]. 5 mg (7% of theory) of the target compound are thus obtained

Workup

  1. extractionextracted twice with 10 ml of ethyl acetate each time
  2. dry with materialThe combined organic phases are dried over sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product is purified by preparative HPLC [Method 10]
  6. custom5 mg (7% of theory) of the target compound are thus obtained

Sources & evidence

ORD record
ord-c08428d5db23445c95029f6fa516d331
Source dataset
uspto-grants-2011_12
Patent number
US08084481B2

Reaction notes

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