Sodium Azide → HCID 59260081, compound

HRID 642977Notes

Reaction equation

HRID 642977 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH2:4].N([O-])=O.[Na+].[N-:14]=[N+:15]=[N-].[Na+]>C(O)(C(F)(F)F)=O.O>[N:4]([C:3]1[CH:5]=[CH:6][C:7]([I:9])=[CH:8][C:2]=1[F:1])=[N+:14]=[N-:15]

Participants

6

Reactant 3

HCID 33557Sodium AzideHCID 1856942-Fluoro-4-iodoanilineHCID 23668193Sodium Nitrite

Product 1

HCID 59260081HCID 59260081, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent2×

Procedure

2-Fluoro-4-iodoaniline (1.1, 6.50 g, 27.4 mmol) was dissolved in 25 mL TFA and stirred in ice bath. Solid NaNO2 (2.07 g, 30.1 mmol) was added in small portions. The resulting mixture was stirred for 30 min in ice bath. Sodium azide (1.87 g, 28.8 mmol) was dissolved in 10 mL water and chilled in ice bath. This cold solution was then added to the TFA solution in three portions. The mixture was stirred in ice bath for 1 hr and concentrated in vacuo to remove TFA. The residue was taken into 600 mL DCM and washed with water three times. The organic phase was dried using MgSO4 and concentrated in vacuo to afford 1-azido-2-fluoro-4-iodobenzene 1.2 as a brownish waxy solid in >99% yield. In the mean time, 5-chlorothiophene-2-carboxylic acid (1.3, 9.13 g, 56 mmol) was dissolved in 200 mL dry DCM along with 0.5 mL dry DMF. To the vigorously stirred solution was carefully added oxalyl chlororide (14.7 mL, 169 mmol) dropwise. The resulting solution was stirred for 3 hrs at RT and concentrated in vacuo. The residue was pumped to dryness and then dissolved in 300 mL dry DCM. To this solution was added propargylamine (5.8 mL, 84 mmol) dropwise. The mixture was stirred at RT overnight during which time solid precipitated out. 600 mL hexane was added and the mixture was vigorously stirred for a few hours. The solid was collected by filtration and washed with hexane to give 5-chloro-N-(prop-2-ynyl)thiophene-2-carboxamide 1.4 (9.47 g, 85%) which was used directly without further purification. MS found for C8H6ClNOS as (M+H)+ 200.0, 202.0 (chlorine pattern).

Workup

  1. stirringThe resulting mixture was stirred for 30 min in ice bath
  2. temperaturechilled in ice bath
  3. stirringThe mixture was stirred in ice bath for 1 hr
  4. concentrationconcentrated in vacuo
  5. customto remove TFA
  6. washwashed with water three times
  7. customThe organic phase was dried
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4293115bd2a647348a68ed1fef349b65
Source dataset
uspto-grants-2010_04
Patent number
US07696352B2

Reaction notes

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