Methoxymethyl-triphenylphosphonium chloride → N-(3-Chloro-4-fluorophenyl)-4-[(E)-2-methoxyvinyl]-1,2,5-oxadiazole-3-carboxamide N-(3-chloro-4-fluorophenyl)-4-[(Z)-2-methoxyvinyl]-1,2,5-oxadiazole-3-carboxamide

HRID 1845781Notes

Reaction equation

HRID 1845781 reaction equation
[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].[Cl:30][C:31]1[CH:32]=[C:33]([NH:38][C:39]([C:41]2[C:45]([CH:46]=O)=[N:44][O:43][N:42]=2)=[O:40])[CH:34]=[CH:35][C:36]=1[F:37]>C1(C)C=CC=CC=1.C1COCC1>[Cl:30][C:31]1[CH:32]=[C:33]([NH:38][C:39]([C:41]2[C:45](/[CH:46]=[CH:2]\[O:3][CH3:4])=[N:44][O:43][N:42]=2)=[O:40])[CH:34]=[CH:35][C:36]=1[F:37].[Cl:30][C:31]1[CH:32]=[C:33]([NH:38][C:39]([C:41]2[C:45](/[CH:46]=[CH:2]/[O:3][CH3:4])=[N:44][O:43][N:42]=2)=[O:40])[CH:34]=[CH:35][C:36]=1[F:37]

Participants

6

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 23676156Sodium t-butoxideHCID 58941813HCID 58941813, compound

Product 1

HCID 86689417N-(3-Chloro-4-fluorophenyl)-4-[(E)-2-methoxyvinyl]-1,2,5-oxadiazole-3-carboxamide N-(3-chloro-4-fluorophenyl)-4-[(Z)-2-methoxyvinyl]-1,2,5-oxadiazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (methoxymethyl)(triphenyl)phosphonium chloride (23.0 g, 66.0 mmol) in toluene (183 mL) was added sodium tert-butoxide (6.60 g, 0.066 mol) at rt under an atmosphere of nitrogen. After stirring for 30 min, a solution of N-(3-chloro-4-fluorophenyl)-4-formyl-1,2,5-oxadiazole-3-carboxamide (7.6 g, 28 mmol) in THF (18 mL) was cannulated into reaction flask. The resulting solution was stirred at rt for 1 h. The reaction was quenched with 1 N HCl and diluted with ethyl acetate and the aqueous layer was extracted with ethyl acetate once. The combined organic solutions were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified with silica gel chromatography (20% ethyl acetate/Hex) to give product (2.0 g 24%, E isomer, 2.6 g, 31%, Z isomer) as white solids. Z isomer: 1H NMR (400 MHz, CDCl3): δ□ 8.54 (s, 1 H) 7.87 (dd, J=6.4, 2.7 Hz, 1 H), 7.42 (m, 1 H), 7.16 (t, J=8.5 Hz, 1 H), 6.66 (d, J=6.6 Hz, 1 H), 6.03 (d, J=6.6 Hz, 1 H), 3.97 (s, 3 H). MF=C12H10ClFN3O3; LCMS for C12H10ClFN3O3(M+H)+: m/z=298.0.

Workup

  1. stirringThe resulting solution was stirred at rt for 1 h
  2. customThe reaction was quenched with 1 N HCl
  3. additiondiluted with ethyl acetate
  4. extractionthe aqueous layer was extracted with ethyl acetate once
  5. washThe combined organic solutions were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified with silica gel chromatography (20% ethyl acetate/Hex)
  10. customto give product (2.0 g 24%, E isomer, 2.6 g, 31%, Z isomer) as white solids

Sources & evidence

ORD record
ord-ba15b76d933c43fb8333aa7de07839f0
Source dataset
uspto-grants-2015_02
Patent number
US08951536B2

Reaction notes

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