Diisopropylethylamine → (2-Fluoro-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)methanol

HRID 1804512Notes

Reaction equation

HRID 1804512 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16](F)=[O:17])[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=1[CH2:30][OH:31])[C:23](=[N:25]O)[NH2:24].CCN(C(C)C)C(C)C>C(#N)C.ClCCl>[F:19][C:20]1[CH:21]=[C:22]([C:23]2[N:25]=[C:16]([C:10]3[O:9][N:8]=[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[C:11]=3[C:12]([F:15])([F:14])[F:13])[O:17][N:24]=2)[CH:27]=[CH:28][C:29]=1[CH2:30][OH:31]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 58374067HCID 58374067, compoundHCID 74865047HCID 74865047, compound

Product 1

HCID 67457612(2-Fluoro-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)methanolYield 50.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A heterogeneous mixture of 3-phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl fluoride (1-E, 0.973 g, 3.75 mmol), 3-fluoro-N′-hydroxy-4-(hydroxymethyl)benzimidamide (0.691 g, 3.75 mmol), and Hunig's Base (0.852 mL, 4.88 mmol) in acetonitrile (7 mL) was stirred at room temperature over the weekend. The reaction mixture was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. The dichloromethane was removed under reduced pressure to give an orange oily residue which was purified by flash silica gel chromatography using a 20% mixture of ethyl acetate in hexane to give (2-fluoro-4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)methanol (0.762 g, 1.88 mmol, 50% yield) as a pale yellow solid. The compound had an HPLC ret. time=3.33 min.−Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=406.1.

Workup

  1. washwashed with a saturated aqueous solution of sodium bicarbonate
  2. dry with materialdried over anhydrous sodium sulfate
  3. customThe dichloromethane was removed under reduced pressure
  4. customto give an orange oily residue which
  5. customwas purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-40af95c089ef4a8dbd5fe73132c6e47e
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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