Sodium Chlorite → HCID 86698608, compound

HRID 338262Notes

Reaction equation

HRID 338262 reaction equation
[C:1]([N:4]1[CH2:8][CH2:7][CH:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][C:23]=3[Cl:24])[NH:20][CH:19]=[C:18]4[CH:25]=[O:26])=[CH:11][CH:10]=2)[CH2:5]1)(=[O:3])[CH3:2].Cl([O-])=[O:28].[Na+].O.O.OP([O-])(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O.CC(=CC)C>[C:1]([N:4]1[CH2:8][CH2:7][CH:6]([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][C:23]=3[Cl:24])[NH:20][CH:19]=[C:18]4[C:25]([OH:28])=[O:26])=[CH:13][CH:14]=2)[CH2:5]1)(=[O:3])[CH3:2]

Participants

8

Reactant 3

HCID 23668197Sodium Chlorite2×HCID 23673460Sodium Phosphate, Monobasic, Dihydrate2×HCID 86698607HCID 86698607, compound

Product 1

HCID 86698608HCID 86698608, compoundYield 40.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolventHCID 105532-Methyl-2-buteneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-[4-(1-acetylpyrrolidin-3-yl)phenyl]-6-chloro-1H-indole-3-carbaldehyde (60 mg, 0.163 mmol) in acetonitrile (3 mL) and tert-butanol (3 mL) was added 2-methyl-2-butene (3 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (164 mg, 1.8 mmol) and sodium phosphate monobasic dihydrate (381 mg, 2.445 mmol) in water (1.5 mL). The reaction mixture was stirred for 2 hours at room temperature and treated with additional sodium chlorite (218 mg, 2.4 mmol) and sodium phosphate monobasic dihydrate (509 g, 3.26 mmol) in water (1.5 mL) and 2-methyl-2-butene (0.5 mL). The resulting mixture was stirred at room temperature for an additional 16 h. The reaction mixture was evaporated in vacuo and the aqueous residue was extracted with EtOAc (3×20 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in DMSO and purified via prep-HPLC to give 5-[4-(1-acetylpyrrolidin-3-yl)phenyl]-6-chloro-1H-indole-3-carboxylic acid (25 mg) as a white solid. MS (ES+) 383.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 11.96 (br, 1H), 8.08 (d, 1H), 7.93 (s, 1H), 7.64 (s, 1H), 7.38 (m, 4H), 3.1-3.9 (m, 5H), 2.2-2.5 (m, 1H), 1.9-2.1 (m, 4H).

Workup

  1. stirringThe resulting mixture was stirred at room temperature for an additional 16 h
  2. customThe reaction mixture was evaporated in vacuo
  3. extractionthe aqueous residue was extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in DMSO
  7. custompurified via prep-HPLC

Sources & evidence

ORD record
ord-71df5cd4109d43df968fff7bfe757fed
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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