Water → 1-Carbamoyl-6-ethyl-1H-indole-3-carboxylic acid

HRID 1527166Notes

Reaction equation

HRID 1527166 reaction equation
[CH2:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:15]=[O:16])=[CH:8][N:9]2[C:12]([NH2:14])=[O:13])=[CH:5][CH:4]=1)[CH3:2].CC(=CC)C.O.[O-:23]Cl=O.[Na+]>C1COCC1.C(O)(C)(C)C>[C:12]([N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([CH2:1][CH3:2])[CH:11]=2)[C:7]([C:15]([OH:23])=[O:16])=[CH:8]1)(=[O:13])[NH2:14]

Participants

7

Reactant 4

HCID 962WaterHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 866737906-Ethyl-3-formyl-indole-1-carboxylic acid amide

Product 1

HCID 682834061-Carbamoyl-6-ethyl-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

6-Ethyl-3-formyl-indole-1-carboxylic acid amide (720 mg, 3.33 mmol) was dissolved in a mixture of THF (60 mL) and t-butanol (18 mL). 2-methyl-2-butene (2 M solution in THF, 66.6 mL, 133 mmol) was added, followed by a water (16 mL) solution of NaClO2 (80%, 3.76 g, 33.3 mmol) and NaH2PO4 (3.20 g, 26.6 mmol). The resulting solution was stirred at RT for 4 h and THF was concentrated. EtOAc was added and the layers separated. The aqueous layer was acidified by addition of HCl 1N and extracted twice with EtOAc. The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (eluent: c-hexane to EtOAc to CH2Cl2/MeOH 8:2) to give the desired compound. tR (HPLC conditions a): 2.17 min. 1H-NMR (400 MHz, CDCl3): δ (ppm): 12.9 (m, 1H), 8.81 (s, 1H), 8.66 (bs, 1H), 8.23 (d, 1H),), 8.09 (m, 2H), 7.70 (dd, 1H).

Workup

  1. concentrationTHF was concentrated
  2. additionEtOAc was added
  3. customthe layers separated
  4. additionThe aqueous layer was acidified by addition of HCl 1N
  5. extractionextracted twice with EtOAc
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by flash column chromatography on silica gel (eluent: c-hexane to EtOAc to CH2Cl2/MeOH 8:2)

Sources & evidence

ORD record
ord-57ffc23845c1456fbb3d33b16fe19551
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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