2-Methyl-2-butene → HCID 86698618, compound

HRID 338271Notes

Reaction equation

HRID 338271 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]([O:19][CH:20]2[CH2:23][O:22][CH2:21]2)=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:30].[Na+].OP([O-])(O)=O.[Na+]>C(#N)C.O.C(O)(C)(C)C>[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]([O:19][CH:20]2[CH2:23][O:22][CH2:21]2)=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 86698617HCID 86698617, compound

Product 1

HCID 86698618HCID 86698618, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Procedure

To a solution of 6-chloro-5-[4-(oxetan-3-yloxy)phenyl]-1H-indole-3-carbaldehyde (100 mg, 0.34 mmol) in acetonitrile (4 mL) was added tert-butanol (4 mL), water (4 mL) and 2-methyl-2-butene (2.52 mL). The reaction mixture was stirred for 2 minutes and treated with sodium chlorite (620 mg, 9.25 mmol) and sodium phosphate monobasic (1.45 g, 9.29 mmol). The mixture was stirred at room temperature for 17 hours. The reaction was quenched with sodium sulfite and the mixture was concentrated in vacuo to give a residue, which was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (2×10 mL), dried over Na2SO4 and concentrated in vacuo to give a residue, which was purified by prep-HPLC to give 6-chloro-5-[4-(oxetan-3-yloxy)phenyl]-1H-indole-3-carboxylic acid (45 mg, 42%) as an off-white solid. MS (ES+) 343.9 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 11.32 (s, 1H), 8.07 (s, 1H), 7.92 (s, 1H), 7.62 (s, 1H), 7.35 (d, 2H), 6.87 (d, 2H), 5.35-5.32 (m, 1H), 4.97-4.94 (m, 2H), 4.61-4.58 (m, 2H).

Workup

  1. stirringThe mixture was stirred at room temperature for 17 hours
  2. customThe reaction was quenched with sodium sulfite
  3. concentrationthe mixture was concentrated in vacuo
  4. customto give a residue, which
  5. extractionwas extracted with ethyl acetate (3×10 mL)
  6. washThe combined organic layers were washed with brine (2×10 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customto give a residue, which
  10. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-170b6dc494ae439abd41261b80feb551
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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