Sodium Azide → 1-Fluoro-2-isocyanato-4-methoxybenzene

HRID 2428034

Reaction equation

HRID 2428034 reaction equation
N/C(/C#N)=C(\N[C:7]([NH:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[F:18])=[O:8])/C#N.FC1C=CC(OC)=CC=1C(O)=O.C(Cl)(=O)C(Cl)=O.[N-]=[N+]=[N-].[Na+]>C(Cl)Cl.CN(C=O)C.O.O1CCOCC1>[F:18][C:11]1[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:10]=1[N:9]=[C:7]=[O:8]

Participants

8

Reactant 4

HCID 33557Sodium AzideHCID 65578Oxalyl chlorideHCID 27745432-Fluoro-5-methoxybenzoic acidHCID 57474799HCID 57474799, compound

Product 1

HCID 221509931-Fluoro-2-isocyanato-4-methoxybenzene

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

(Z)-1-(2-Amino-1,2-dicyanovinyl)-3-(2-fluoro-5-methoxyphenyl)urea. 2-Fluoro-5-methoxybenzoic acid (0.62 g, 3.62 mmol) was dissolved in CH2Cl2 (15 mL) and DMF (0.5 mL). Oxalyl chloride (0.38 mL, 4.32 mmol) was added dropwise. The mixture was stirred for another 15 min. The reaction was concentrated and then taken up in dioxane (10 mL). Sodium azide (0.26 g, 3.96 mmol) in water/dioxane (1:1 v/v, 10 mL) was added to the acid chloride at 0° C. The mixture was stirred for 10 min. The reaction was partitioned between EtOAc and water. The layers were shaken and separated. The organic layer was dried over sodium sulfate, filtered, and concentrated. The crude acyl azide was filtered through a silica gel plug (90% Hexanes in EtOAc. The filtrate was concentrated. The purified acyl azide was dissolved in toluene and stirred at 100° C. for 1 h. The toluene solution was concentrated to afford 1-fluoro-2-isocyanato-4-methoxybenzene in quantitative yield. 1-Fluoro-2-isocyanato-4-methoxybenzene (0.6 g, 3.62 mmol) was reacted with 2,3-diaminomaleonitrile (0.39 g, 3.62 mmol) according to General Procedure A to afford the title compound. MS (ESI) m/z 276.4 [M+1]+.

Workup

  1. concentrationThe reaction was concentrated
  2. stirringThe mixture was stirred for 10 min
  3. customThe reaction was partitioned between EtOAc and water
  4. stirringThe layers were shaken
  5. customseparated
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. filtrationThe crude acyl azide was filtered through a silica gel plug (90% Hexanes in EtOAc
  10. concentrationThe filtrate was concentrated
  11. dissolutionThe purified acyl azide was dissolved in toluene
  12. stirringstirred at 100° C. for 1 h
  13. concentrationThe toluene solution was concentrated

Sources & evidence

ORD record
ord-7cf7958bb9a04a3da68198bc2ae11b0a
Source dataset
uspto-grants-2011_06
Patent number
US07968556B2

Linked notes

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