Hydrochloric Acid → Lesinurad

HRID 885595Notes

Reaction equation

HRID 885595 reaction equation
[OH-].[Li+].[Br:3][C:4]1[N:5]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]([CH:25]3[CH2:27][CH2:26]3)=[CH:17][CH:16]=2)[C:6]([S:9][CH2:10][C:11]([O:13]C)=[O:12])=[N:7][N:8]=1.Cl>O.C(O)C.C1COCC1>[Br:3][C:4]1[N:5]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]([CH:25]3[CH2:27][CH2:26]3)=[CH:17][CH:16]=2)[C:6]([S:9][CH2:10][C:11]([OH:13])=[O:12])=[N:7][N:8]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 57811446Methyl 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)acetate

Product 1

HCID 53465279LesinuradYield 93.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of lithium hydroxide (98 mg, 4.1 mmol) in water (10 mL) was added dropwise over 5 mins to a solution of methyl 2-(5-bromo-4-(1-cyclopropylnaphthalen-4-yl)-4H-1,2,4-triazol-3-ylthio)acetate (prepared as described in example 1 above; 1.14 g, 2.7 mmol) in ethanol (10 mL) and THF (10 mL) at 0° C. The mixture was stirred at 0° C. for a further 45 mins and then neutralized to pH 7 by the addition of 0.5N HCl solution at 0° C. The resulting mixture was concentrated in vacuo to ⅕th of its original volume, then diluted with water (˜20 mL) and acidified to pH 2-3 by the addition of 0.5N HCl to produce a sticky solid. (If the product comes out as an oil during acidification, extraction with DCM is recommended.) The tan solid was collected by vacuum filtration and dried under high vacuum at 50° C. for 16 h in the presence of P2O5 to yield 2-(5-bromo-4-(1-cyclopropylnaphthalen-4-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid (1.02 g, 93%).

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo to ⅕th of its original volume
  2. additiondiluted with water (˜20 mL)
  3. additionacidified to pH 2-3 by the addition of 0.5N HCl
  4. customto produce a sticky solid
  5. extraction(If the product comes out as an oil during acidification, extraction with DCM
  6. filtration) The tan solid was collected by vacuum filtration
  7. dry with materialdried under high vacuum at 50° C. for 16 h in the presence of P2O5

Sources & evidence

ORD record
ord-df1a0437396040b7be823497a735fb03
Source dataset
uspto-grants-2012_08
Patent number
US08242154B2

Reaction notes

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