Water → 5-Amino-2-fluoroisonicotinic acid

HRID 428363

Reaction equation

HRID 428363 reaction equation
C(OC([NH:8][C:9]1[C:10]([C:16]([OH:18])=[O:17])=[CH:11][C:12]([F:15])=[N:13][CH:14]=1)=O)(C)(C)C.O.FC(F)(F)C(O)=O>ClCCl>[NH2:8][C:9]1[C:10]([C:16]([OH:18])=[O:17])=[CH:11][C:12]([F:15])=[N:13][CH:14]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 106110655-((tert-Butoxycarbonyl)amino)-2-fluoroisonicotinic acid

Product 1

HCID 27625115-Amino-2-fluoroisonicotinic acidYield 86.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 36.6 g (140 mM) of 5-[N-(tert-butoxycarbonyl) amino]-2-fluoropyridine-4-carboxylic acid hydrated with 0.3 equivalents of water in 280 mL of dichloromethane was cooled in an ice bath then treated dropwise over 15 minutes with 140 mL of trifluoroacetic acid. The bath was removed, and the resultant mixture was stirred at room temperature for 14 hours, then concentrated. The yellow-orange solids were triturated in 125 mL of warm 1:1 diethyl ether:dichloromethane. After cooling, the yellow solids were collected, washed with 100 mL of the diethyl ether:dichloromethane mixture, and dried to afford 19.3 g of product. Processing of the filtrate afforded 1.7 g of a second crop. Total yield=21 g (94%). Recrystallization of a small sample from ethyl acetate provided product of mp 259° C. (dec). 1H NMR [(CD3)2SO]: δ8.86 (m, 3H), 7.81 (d, JH-F=1.1 Hz, 1H), 7.20 (d, JH-F=2.3 Hz, 1H).

Workup

  1. temperaturewas cooled in an ice bath
  2. customThe bath was removed
  3. concentrationconcentrated
  4. customThe yellow-orange solids were triturated in 125 mL
  5. temperatureof warm 1:1 diethyl ether
  6. temperatureAfter cooling
  7. customthe yellow solids were collected
  8. washwashed with 100 mL of the diethyl ether
  9. dry with materialdichloromethane mixture, and dried

Sources & evidence

ORD record
ord-f1272beaae7f4746864ad6b59198cac3
Source dataset
uspto-grants-2001_11
Patent number
US06313292B1

Linked notes

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