Benzbromarone → HCID 10282662, compound

HRID 1841297Notes

Reaction equation

HRID 1841297 reaction equation
[CH3:1][CH2:2][C:3]1[O:11][C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:4]=1[C:12]([C:14]1[CH:15]=[C:16]([Br:22])[C:17]([OH:21])=[C:18]([Br:20])[CH:19]=1)=[O:13].C1COCC1.Cl[S:29]([C:32]1[CH:40]=[CH:39][C:35]([C:36]([OH:38])=[O:37])=[C:34]([OH:41])[CH:33]=1)(=[O:31])=[O:30]>C([O-])(O)=O.[Na+]>[Br:22][C:16]1[CH:15]=[C:14]([C:12]([C:4]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=3[O:11][C:3]=2[CH2:2][CH3:1])=[O:13])[CH:19]=[C:18]([Br:20])[C:17]=1[O:21][S:29]([C:32]1[CH:40]=[CH:39][C:35]([C:36]([OH:38])=[O:37])=[C:34]([OH:41])[CH:33]=1)(=[O:31])=[O:30]

Participants

5

Reactant 3

HCID 2333BenzbromaroneHCID 8028TetrahydrofuranHCID 146685314-(Chlorosulfonyl)-2-hydroxybenzoic acid2×

Product 1

HCID 10282662HCID 10282662, compoundYield 39.1%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent3×

Procedure

At ambient temperature, to a stirred solution of commercial benzbromarone (0.243 g, 0.574 mmol) in 0.5M aq. NaHCO3:THF (8 mL; 1:1) was added portionwise 4-chiorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After the addition was complete the reaction was stirred for 18 h. To the reaction was added 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After 2 h, the reaction was quenched with 2N HCl (25 mL), extracted with EtOAc and concentrated. The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H20 containing 0.1% TFA) and crystallized from EtOAc/hexane to give 0.14 g (39%) of the title compound as a white solid, mp 173° C.; 1H NMR (DMSO-d6) δ1.25 (t, 3 H), 2.76 (q, 2 H), 7.30 (dt, 1 H), 7.36 (dt, 1 H), 7.44-7.49 (m, 3 H), 7.66 (d, 1 H), 8.03 (d, 1 H), 8.08 (s, 2 H). IR (KBr) 3400, 2950, 1680, 1650, 1400 and 1180 cm−1. mass spectrum (−ESI), m/z 621/623/625 (M−H). Anal. Calcd. for C24H16Br2O8S: C, 46.18; H, 2.58; N, 0.00. Found: C, 46.41; H, 2.64; N, 0.00.

Workup

  1. temperaturewhile maintaining the pH at 8
  2. additionAfter the addition
  3. temperaturewhile maintaining the pH at 8
  4. waitAfter 2 h
  5. customthe reaction was quenched with 2N HCl (25 mL)
  6. extractionextracted with EtOAc
  7. concentrationconcentrated
  8. customThe crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H20 containing 0.1% TFA)
  9. customcrystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-998e421b7b974751967af31c57e3f6f7
Source dataset
uspto-grants-2004_01
Patent number
US06683107B2

Reaction notes

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