Hydrochloric Acid → 6-Bromo-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acid

HRID 338387Notes

Reaction equation

HRID 338387 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13]C)=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[OH:27])=[CH:17][CH:16]=1.[OH-].[Na+].Cl.O1CCOCC1>CO>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[OH:27])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 312751,4-DioxaneHCID 86698726Methyl 6-bromo-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylate

Product 1

HCID 866987286-Bromo-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acidYield 8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a semi suspension of crude methyl 6-bromo-5-(2′-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylate (120 mg, 0.284 mmol) in methanol (4 ml) was added 1N NaOH (1 mL, 1 mmol) then heated to 70° C. for 16 hrs. 5N NaOH (1 mL, 5 mmol) was then added and heating continued for 24 hrs. The reaction was cooled and quenched with 4N HCl in dioxane (2 ml, 8 mmol) then concentrated to give a brown solid which was purified by reverse phase preparative HPLC to afford the title compound as a tan solid (9 mg, 8%) MS (AP−) 406.0 (M−H)−. 1H NMR (400 MHz, MeOH-d4) δ: 8.10 (s, 1H), 7.99 (s, 1H), 7.80 (s, 1H), 7.63 (d, 2H), 7.46 (d, 2H), 7.35 (dd, 1H), 7.17 (td, 1H), 6.86-6.98 (m, 2H).

Workup

  1. temperatureheating
  2. temperatureThe reaction was cooled
  3. concentrationthen concentrated
  4. customto give a brown solid which
  5. customwas purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-cc9f464582cb44d5bb47f0f35d80f85e
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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