Toluene → HCID 69099538, compound

HRID 2251575Notes

Reaction equation

HRID 2251575 reaction equation
[NH2:1]/[C:2](/[N:5]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1)[CH2:6][CH2:7][C:8]1[CH:22]=[CH:21][C:11]([O:12][C:13]([CH3:20])([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:10][CH:9]=1)=[N:3]\[OH:4].C(N(CC)CC)C.[C:41](Cl)(=O)[CH:42]([CH3:44])[CH3:43].C1(C)C=CC=CC=1>ClCCl>[CH:42]([C:44]1[O:4][N:3]=[C:2]([N:5]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:31])([F:32])[F:33])=[CH:26][CH:25]=2)[CH2:6][CH2:7][C:8]2[CH:22]=[CH:21][C:11]([O:12][C:13]([CH3:19])([CH3:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:10][CH:9]=2)[N:1]=1)([CH3:43])[CH3:41]

Participants

6

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 59643441HCID 59643441, compound

Product 1

HCID 69099538HCID 69099538, compoundYield 46.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of ethyl 2-[4-(2-{[(E)-amino(hydroxyimino)methyl][4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate (1 g; 2.14 mmol) and triethylamine (0.30 ml; 2.14 mmol) in 10 ml of dichloromethane was cooled in an ice bath and treated under nitrogen with isobutyryl chloride (0.20 ml; 1.93 mmol). The mixture was allowed to warm to rt. After 1 hr, 8 ml of toluene were added and the reaction mixture was heated to 110C under a reflux condenser. After 5 hr, it was partitioned between ethyl acetate and 0.5N HCl. The organic phase was washed with 0.5 N HCl (twice), 1N NaOH (three times) and brine, dried over sodium sulfate and concentrated. Purification by flash chromatography using ethyl acetate-hexane mixtures (5–50% gradient) afforded ethyl 2-[4-(2-{(5-isopropyl-1,2,4-oxadiazol-3-yl)[4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate (470 mg; 43% yield).

Workup

  1. waitAfter 5 hr
  2. customit was partitioned between ethyl acetate and 0.5N HCl
  3. washThe organic phase was washed with 0.5 N HCl (twice), 1N NaOH (three times) and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification by flash chromatography

Sources & evidence

ORD record
ord-238eef4576884e549de7975f25363131
Source dataset
uspto-grants-2008_01
Patent number
US07319104B2

Reaction notes

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