Acetic Acid → (5-Chloro-2-dimethylaminomethyl-1H-indol-4-yl)-acetic acid ethyl ester

HRID 1161888Notes

Reaction equation

HRID 1161888 reaction equation
COC([N:5]1[C:13]2[C:8](=[C:9]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:10]([Cl:14])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH:21]=O)=O.[CH3:23][NH:24][CH3:25].C([BH3-])#N.[Na+].C(O)(=O)C.C([O-])(O)=O.[Na+]>C1COCC1.CCO.CO.CCOC(C)=O>[CH2:19]([O:18][C:16](=[O:17])[CH2:15][C:9]1[C:10]([Cl:14])=[CH:11][CH:12]=[C:13]2[C:8]=1[CH:7]=[C:6]([CH2:21][N:24]([CH3:25])[CH3:23])[NH:5]2)[CH3:20]

Participants

10

Reactant 5

HCID 176Acetic AcidHCID 674DimethylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 866038735-Chloro-4-ethoxycarbonylmethyl-2-formyl-indole-1-carboxylic acid methyl ester

Product 1

HCID 66820374(5-Chloro-2-dimethylaminomethyl-1H-indol-4-yl)-acetic acid ethyl ester

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Chloro-4-ethoxycarbonylmethyl-2-formyl-indole-1-carboxylic acid methyl ester (350 mg, 1.08 mmol) is dissolved in dry THF (10 ml) under an atmosphere of argon, and dimethylamine (290 microL of a 5.6 M solution in EtOH, 1.62 mmol) is added at RT. The reaction mixture is stirred at RT for 18 hours. A solution of sodium cyanoborohydride (82 mg, 1.29 mmol) in methanol (3 ml) and acetic acid (310 microL, 5.40 mmol) is then added. Stirring is continued for 3 hours at RT. TLC analysis indicates complete conversion of the starting material. The reaction mixture is diluted with EtOAc and poured on water. The pH is made alkaline by the addition of a saturated aqueous solution of NaHCO3. The aqueous layer is extracted with EtOAc, and the combined organic layers are washed once with concentrated aqueous NaCl solution. After drying over Na2SO4, the solvent is removed and the residue is purified by FCC (CH2Cl2/EtOH/aq. NH3 90:9:1) to give the title compound. 1H NMR (DMSO, 400 MHz) δ 1.19 (t, J=6.6 Hz, 3H), 2.20 (s, 6H), 3.55 (s, 2H), 3.97 (s, 2H), 4.11 (q, J=6.6 Hz, 2H), 6.38 (s, 1H), 7.08 (d, J=9.0 Hz, 1H), 7.26 (d, J=9.0 Hz, 1H), 11.2 (br s, 1H); ES-MS: 293.2 [M+H]−.

Workup

  1. stirringStirring
  2. waitis continued for 3 hours at RT
  3. additionpoured on water
  4. extractionThe aqueous layer is extracted with EtOAc
  5. washthe combined organic layers are washed once with concentrated aqueous NaCl solution
  6. dry with materialAfter drying over Na2SO4
  7. customthe solvent is removed
  8. customthe residue is purified by FCC (CH2Cl2/EtOH/aq. NH3 90:9:1)

Sources & evidence

ORD record
ord-786cb597bc284f3bb6ccb659d832e6a9
Source dataset
uspto-grants-2010_10
Patent number
US07820672B2

Reaction notes

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