Hydrochloric Acid → 2-Fluoro-4-iodopyridine-3-carboxylic acid

HRID 415920Notes

Reaction equation

HRID 415920 reaction equation
[F:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6]([I:10])[CH:5]=[CH:4][N:3]=1.CC(=CC)C.P([O-])([O-])([O-])=[O:17].[Na+].[Na+].[Na+].Cl([O-])=O.[Na+].Cl>C(O)(C)(C)C.O.ClCCl>[F:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]([I:10])[C:7]=1[C:8]([OH:17])=[O:9]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 105532-Methyl-2-buteneHCID 24243Trisodium PhosphateHCID 99923282-Fluoro-4-iodopyridine-3-carbaldehydeHCID 23668197Sodium Chlorite

Product 1

HCID 447547542-Fluoro-4-iodopyridine-3-carboxylic acidYield 100%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Procedure

To a stirred solution of 2-fluoro-4-iodopyridine-3-carboxaldehyde (10.0 g, 39.8 mmol) in tert-butanol (350 mL) and water (100 mL) at room temperature were added 2-methyl-2-butene (42.1 ml, 398 mmol), sodium phosphate, monobasic, monohydrate (60.5 g, 438 mmol) and sodium chlorite (18.0 g, 199 mmol). The reaction mixture was stirred at room temperature for 75 min. The reaction mixture was diluted with dichloromethane and a 6M aqueous solution of hydrochloric acid was added until pH ˜2. The water layer was extracted with dichloromethane. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. Purification by MPLC (CH2Cl2/MeOH+1% AcOH: 100/0 to 80/20) afforded 2-fluoro-4-iodonicotinic acid (10.63 g, 39.8 mmol, 100% yield). MS (ESI pos. ion) m/z: 268 (MH+). Calc'd exact mass for C6H3FINO2: 267.

Workup

  1. extractionThe water layer was extracted with dichloromethane
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by MPLC (CH2Cl2/MeOH+1% AcOH: 100/0 to 80/20)

Sources & evidence

ORD record
ord-5d2c5678c7e9485792845aff230869be
Source dataset
uspto-grants-2012_01
Patent number
US08088794B2

Reaction notes

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