Carbon Dioxide → 5-(2-Fluoro-6-iodophenyl)-3-methyl-1,2,4-oxadiazole

HRID 1524883Notes

Reaction equation

HRID 1524883 reaction equation
[F:1][C:2]1[CH:14]=[CH:13][CH:12]=[C:11]([I:15])[C:3]=1[C:4]([O:6]/[N:7]=[C:8](\[NH2:10])/[CH3:9])=O.[C:16]([O-:19])(=[O:18])[CH3:17].[Na+].[F:21][C:22]1[CH:27]=[CH:26][CH:25]=C(I)[C:23]=1[C:29]1[O:33][N:32]=[C:31]([CH3:34])[N:30]=1.C([Mg]Cl)(C)C.C(=O)=O>C1COCC1.C(O)(C)(C)C>[F:1][C:2]1[CH:14]=[CH:13][CH:12]=[C:11]([I:15])[C:3]=1[C:4]1[O:6][N:7]=[C:8]([CH3:9])[N:10]=1.[F:21][C:22]1[C:23]([C:29]2[O:33][N:32]=[C:31]([CH3:34])[N:30]=2)=[C:17]([CH:25]=[CH:26][CH:27]=1)[C:16]([OH:19])=[O:18]

Participants

9

Reactant 5

HCID 280Carbon DioxideHCID 517045Sodium AcetateHCID 161029005-(2-Fluoro-6-iodophenyl)-3-methyl-1,2,4-oxadiazoleHCID 87262981[(Z)-1-aminoethylideneamino] 2-fluoro-6-iodobenzoateHCID 178418918HCID 178418918, compound

Product 2

HCID 161029005-(2-Fluoro-6-iodophenyl)-3-methyl-1,2,4-oxadiazoleHCID 670865883-Fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Alternately, acid (XXXa) is prepared by first converting 2-fluoro-6-iodobenzoic acid to the acid chloride by reaction with a chlorinating agent such as oxalyl chloride, in a solvent such as DCM, with a catalytic amount of DMF, at a temperature of 0° C. Subsequent reaction of the acid chloride with N-hydroxyacetamide in a solvent such as CH2Cl2 provides (Z)—N′-((2-fluoro-6-iodobenzoyl)oxy)acetimidamide. 5-(2-Fluoro-6-iodophenyl)-3-methyl-1,2,4-oxadiazole is prepared by reacting (Z)—N′-((2-fluoro-6-iodobenzoyl)oxy)acetimidamide with sodium acetate, in a solvent such as tert-butanol, at temperatures ranging from 100° C. to 110° C. 3-Fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid (XXXa) is prepared by reacting 5-(2-fluoro-6-iodophenyl)-3-methyl-1,2,4-oxadiazole with a grignard reagent such as i-PrMgCl, in a suitable solvent such as THF and the like, at a temperature of −78° C. Subsequent addition of CO2 gas, at a temperature of −78° C. provides 3-fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid (XXXa).

Workup

  1. customranging from 100° C. to 110° C
  2. custom3-Fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid (XXXa) is prepared
  3. customat a temperature of −78° C

Sources & evidence

ORD record
ord-639e8893b2dc4f948c93a78917987d5c
Source dataset
uspto-grants-2015_07
Patent number
US09079911B2

Reaction notes

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