Hydrochloric Acid → 4-Amino-3-chloro-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoropicolinic acid

HRID 1754141Notes

Reaction equation

HRID 1754141 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([CH:16]([F:18])[CH3:17])[C:10]=2[F:19])[N:5]=[C:4]([C:20]([OH:22])=[O:21])[C:3]=1[Cl:23].[OH-].[Na+].[NH2:26][C:27]1[C:32]([F:33])=[C:31]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([CH:41]([F:43])[CH3:42])[C:35]=2[F:44])[N:30]=[C:29]([C:45]([O:47]C)=[O:46])[C:28]=1[Cl:49].Cl>CO>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([CH:16]([F:18])[CH3:17])[C:10]=2[F:19])[N:5]=[C:4]([C:20]([O:22][CH2:31][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:21])[C:3]=1[Cl:23].[NH2:26][C:27]1[C:32]([F:33])=[C:31]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([CH:41]([F:43])[CH3:42])[C:35]=2[F:44])[N:30]=[C:29]([C:45]([OH:47])=[O:46])[C:28]=1[Cl:49]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 704976444-Amino-3-chloro-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoropicolinic acidHCID 70497684Methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoropicolinate

Product 2

HCID 70497598Benzyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoropicolinateHCID 704976444-Amino-3-chloro-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoropicolinic acidYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

4-Amino-3-chloro-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoropicolinic acid. A 2 molar (M) solution of aqueous sodium hydroxide (NaOH; 580 μL, 1.2 mmol, 4.0 equiv) was added to a stirred suspension of methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoropicolinate (110 mg, 0.29 mmol, 1.0 equiv) in methyl alcohol (1.9 mL) at 23° C. The resulting homogeneous pale yellow solution was stirred at 23° C. for 20 h. The reaction mixture was adjusted to approximately pH=4 via dropwise addition of concentrated hydrochloric acid (HCl) and concentrated via rotary evaporation. The residue was slurried in water and vacuum filtered to afford the desired product, 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoropicolinic acid as a white powder (55 mg, 50%): IR (thin film) 3319 (m), 3193 (w), 2983 (w), 1719 (m), 1629 (s) cm−1; 1H NMR (300 MHz, DMSO-d6) δ 7.58 (t, J=9 Hz, 1H), 7.49 (d, J=9 Hz, 1H), 6.99 (br s, 2H), 6.15 (dq, J=44, 7 Hz, 1H), 1.71 (dd, J=23, 7 Hz, 3H); ESIMS m/z 365 ([M+H]+).

Workup

  1. concentrationconcentrated via rotary evaporation
  2. filtrationvacuum filtered

Sources & evidence

ORD record
ord-e3c701fa3a6249dcac75ab151055ceca
Source dataset
uspto-grants-2015_10
Patent number
US09169217B2

Reaction notes

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