2-Methyl-2-butene → 6-Chloro-5-(4-(3-hydroxyoxetan-3-yl)phenyl)-1H-indole-3-carboxylic acid

HRID 1054571Notes

Reaction equation

HRID 1054571 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:18]=[CH:17][C:16]([C:19]2([OH:23])[CH2:22][O:21][CH2:20]2)=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:30].[Na+].O.OP([O-])(O)=O.[Na+]>CC#N.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:30])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2([OH:23])[CH2:22][O:21][CH2:20]2)=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium ChloriteHCID 866985766-chloro-5-(4-(3-hydroxyoxetan-3-yl)phenyl)-1H-indole-3-carbaldehyde

Product 1

HCID 866985776-Chloro-5-(4-(3-hydroxyoxetan-3-yl)phenyl)-1H-indole-3-carboxylic acidYield 34.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To the mixture of 6-chloro-5-[4-(3-hydroxy-oxetan-3-yl)-phenyl]-1H-indole-3-carbaldehyde (50.0 mg, 0.15 mmol) in MeCN (2 mL) was added 2-methyl-2-butene (2.0 mL, 13.7 mmol), followed by sodium chlorite (138 mg, 1.53 mmol) and sodium phosphate monobasic hydrate (211.0 mg, 1.53 mmol) in water (1 mL). The reaction mixture was stirred at room temperature for 20 hours, and concentrated in vacuo. The residue was acidified with 1 N aqueous citric acid (1 mL) and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (34-80% EtOAc/heptanes, with 0.2% formic acid modifier) to afford the title compound (18 mg, 34%) as a brown solid. MS (ES−) 342.3 (M−H)−. 1H NMR (400 MHz, CD3OD) δ 8.02 (s, 1 H), 7.98 (s, 1 H), 7.66 (d, J=8.20 Hz, 2 H), 7.56 (s, 1 H), 7.47 (d, J=8.20 Hz, 2 H), 4.87-4.80 (m, 4 H).

Workup

  1. concentrationconcentrated in vacuo
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (34-80% EtOAc/heptanes, with 0.2% formic acid modifier)

Sources & evidence

ORD record
ord-29ee36c8b02c40e68e0388e879376619
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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