Hydrogen iodide → Methyl 4-amino-2-(trifluoromethyl)nicotinate

HRID 1170896Notes

Reaction equation

HRID 1170896 reaction equation
I.[N:2]([C:5]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([C:15]([F:18])([F:17])[F:16])[N:8]=[CH:7][CH:6]=1)=[N+]=[N-]>ClCCl>[NH2:2][C:5]1[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([C:15]([F:18])([F:16])[F:17])[N:8]=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 24841Hydrogen iodideHCID 59553876Methyl 4-azido-2-(trifluoromethyl)nicotinate

Product 1

HCID 59553883Methyl 4-amino-2-(trifluoromethyl)nicotinateYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cold (0° C. ice bath) concentrated hydriodic acid (182 mL of a 57% aqueous solution) is added to methyl 4-azido-2-(trifluoromethyl)nicotinate (7.50 g, 30.5 mmol) in a flask. The mixture is stirred at 0° C. until TLC (ethyl acetate-hexanes, 75:25) shows complete consumption of starting material. The mixture is poured over an ice cold solution of potassium hydroxide (95 g of solid KOH dissolved in 300 mL of water). The mixture is extracted with diethyl ether. The ethereal layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford a yellow solid. The solid is dissolved in a minimal amount of dichloromethane and passed through a silica gel plug, eluting with ethyl acetate-hexanes (10:90). The eluant is concentrated to afford 3.42 g (51%) of methyl 4-amino-2-(trifluoromethyl)nicotinate as an off-white solid. 1HNMR (400 MHz, CD3OD), 8.11 (d, 1H), 6.93 (d, 1H), 3.878 (s, 3H). LC/MS (M+1)=221.2

Workup

  1. customconsumption of starting material
  2. additionThe mixture is poured over an ice cold solution of potassium hydroxide (95 g of solid KOH dissolved in 300 mL of water)
  3. extractionThe mixture is extracted with diethyl ether
  4. washThe ethereal layer is washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a yellow solid
  9. washeluting with ethyl acetate-hexanes (10:90)
  10. concentrationThe eluant is concentrated

Sources & evidence

ORD record
ord-a859611002f64a0da1ddd2bde5f4a84e
Source dataset
uspto-grants-2010_11
Patent number
US07829572B2

Reaction notes

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