Potassium Carbonate → 1H-Indolamine

HRID 966492Notes

Reaction equation

HRID 966492 reaction equation
C(OC([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](CCOS(C)(=O)=O)[CH:18]=2)[NH:13][C:12]=1C)=O)C1C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].Cl.[NH:35]1CCC1>O1CCOCC1>[NH:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=[C:12]1[NH2:35]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12308726Azetidine hydrochlorideHCID 233938525-(2-Methanesulfonyloxy-ethyl)-2-methyl-1H-indole-3-carboxylic Acid Benzyl Ester

Product 1

HCID 1220741H-IndolamineYield 29.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

5-(2-Methanesulfonyloxy-ethyl)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.300 g, 0.770 mmol, 1 eq, Example 56, Step D) was suspended in dioxane (20 mL) under Ar. K2CO3 (0.320 g, 2.320 mmol, 3 eq) was added followed by the addition of azetidine hydrochloride (0.217 g, 2.320 mmol, 3 eq). The reaction mixture was stirred and heated to reflux for 18 hours. Then the reaction was quenched with saturated sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic phases were washed with brine and dried over Na2SO4. After removing the solvent, the residue was loaded on silica gel and chromatographed, eluting with ethyl acetate/methanol/triethyl amine (100/10/1). 0.030 g (11%) of the indole-amine was obtained as a white solid. This was converted to the .HCl salt. LC/MS (ESI+) 349 (M+1); Anal. Calcd for C22H24N2O2.1HCl.0.75H2O: C, 73.00; H, 7.10; N, 7.74; Found: C, 73.06; H, 6.95; N, 7.51.

Workup

  1. temperatureheated
  2. temperatureto reflux for 18 hours
  3. customThen the reaction was quenched with saturated sodium bicarbonate
  4. extractionextracted with ethyl acetate (3×)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. customAfter removing the solvent
  8. customchromatographed
  9. washeluting with ethyl acetate/methanol/triethyl amine (100/10/1)

Sources & evidence

ORD record
ord-70243ef1deb240b2b3dc622365cb9747
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

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