2-Methyl-2-butene → 5-[4-(2-amino-2-oxoethoxy)phenyl]-6-chloro-1H-indole-3-carboxylic acid

HRID 338392Notes

Reaction equation

HRID 338392 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:23]=[CH:22][C:16]([O:17][CH2:18][C:19]([NH2:21])=[O:20])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:30].[Na+].O.OP([O-])(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O>[NH2:21][C:19](=[O:20])[CH2:18][O:17][C:16]1[CH:15]=[CH:14][C:13]([C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[Cl:1])[NH:8][CH:7]=[C:6]3[C:11]([OH:30])=[O:12])=[CH:23][CH:22]=1

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium ChloriteHCID 866987342-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenoxy]acetamide

Product 1

HCID 866987355-[4-(2-amino-2-oxoethoxy)phenyl]-6-chloro-1H-indole-3-carboxylic acidYield 21.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenoxy]acetamide (100 mg, 0.30 mmol) in acetonitrile (5 mL) and tert-butanol (5 mL) was added 2-methyl-2-butene (4 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (540 mg, 6.00 mmol) and sodium phosphate monobasic hydrate (850 mg, 6.00 mmol) in water (5 mL) dropwise via additional funnel. The ice bath was removed and the reaction was stirred at room temperature for 48 h. The solvent was removed in vacuo to give a residue, which was purified by prep-HPLC (Prep-HPLC: Column: Kromasil Eternity-5-C18 150*30 mm*5 μm Mobile phase: from 24% MeCN in water (0.225% FA) to 34% MeCN in water (0.225% FA); Wavelength: 220 nm Flow rate: 30 mL/min) to give 5-[4-(2-amino-2-oxoethoxy)phenyl]-6-chloro-1H-indole-3-carboxylic acid (22 mg, 20% yield) as a white solid. MS (ES+) 344.8 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.01-7.99 (m, 2H), 7.57 (s, 1H), 7.43-7.39 (m, 2H), 7.07-7.05 (m, 2H), 4.56 (s, 2H).

Workup

  1. customThe ice bath was removed
  2. customThe solvent was removed in vacuo
  3. customto give a residue, which
  4. customwas purified by prep-HPLC (Prep-HPLC: Column: Kromasil Eternity-5-C18 150*30 mm*5 μm Mobile phase: from 24% MeCN in water (0.225% FA) to 34% MeCN in water (0.225% FA); Wavelength: 220 nm Flow rate: 30 mL/min)

Sources & evidence

ORD record
ord-6f1f1b8481d4483fa75d5a888c13d9fd
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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