Lithium Hydroxide → 4-(2-Chloro-5-fluoro-benzoylamino)-3-methoxy-benzoic acid

HRID 2246067Notes

Reaction equation

HRID 2246067 reaction equation
[Li+].[OH-].C[O:4][C:5](=[O:25])[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:22])[C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[Cl:21])=[C:8]([O:23][CH3:24])[CH:7]=1>O.O1CCCC1>[Cl:21][C:15]1[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:14]=1[C:13]([NH:12][C:9]1[CH:10]=[CH:11][C:6]([C:5]([OH:25])=[O:4])=[CH:7][C:8]=1[O:23][CH3:24])=[O:22]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 59218070Methyl 4-(2-chloro-5-fluoro-benzoylamino)-3-methoxybenzoate

Product 1

HCID 592180674-(2-Chloro-5-fluoro-benzoylamino)-3-methoxy-benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

LiOH (14.1 g, 0.59 mol, 1.1 equiv.) dissolved in H2O (200 mL) was added drop-wise over 45 minutes to a solution of 34 (180 g, 0.53 mol, 1 equiv.) in tetrahydrofuran (1800 mL) at room temperature. The reaction mixture was stirred at room temperature for 16 h. The solvent was evaporated under reduced pressure and the residue re-dissolved in water (ca. 3 L). The insoluble solid was filtered off. Under vigorous stirring, the aqueous filtrate solution was acidified with concentrated HCl aqueous solution (37%) until pH<2. The resulting white solid precipitate was filtered and washed with water. The wet filter cake was then transferred to a flask and dried on rotary evaporator under vacuum at 50° C. overnight to yield 4-(2-chloro-5-fluoro-benzoylamino)-3-methoxy-benzoic acid 35 as a dry, fine white powder. 1H NMR (400 MHz, DMSO-d6) δ: 12.90 (s, 1H), 10.01 (s, 1H), 8.22 (d, 1H), 7.65-7.45 (m, 4H), 7.45-7.30 (m, 1H), 3.88 (s, 1H). MS (ES) m/z 322.0 (MH)+.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe residue re-dissolved in water (ca. 3 L)
  3. filtrationThe insoluble solid was filtered off
  4. filtrationThe resulting white solid precipitate was filtered
  5. washwashed with water
  6. customThe wet filter cake was then transferred to a flask
  7. customdried on rotary evaporator under vacuum at 50° C. overnight

Sources & evidence

ORD record
ord-997ec5562a32446a81ea08a51a76906f
Source dataset
uspto-grants-2010_03
Patent number
US07687494B2

Reaction notes

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