Acetic Acid → 6-(2,3-dimethyl-5-sulfo-3H-indol-3-yl)hexanoic acid

HRID 1667361

Reaction equation

HRID 1667361 reaction equation
C([N:3]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([OH:15])(=[O:14])=[O:13])=[CH:9][CH:10]=2)[C:5]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])([CH3:16])[CH:4]1[CH3:25])C.Br.C(O)(=O)C.C(OC(OCC)C=C)C>C(O)C>[CH3:25][C:4]1[C:5]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])([CH3:16])[C:6]2[C:11](=[CH:10][CH:9]=[C:8]([S:12]([OH:15])(=[O:14])=[O:13])[CH:7]=2)[N:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 624773,3-Diethoxy-1-propeneHCID 866035256-(1-ethyl-2,3-dimethyl-5-sulfo-3H-indol-3-yl)hexanoic acid

Product 1

HCID 598554226-(2,3-dimethyl-5-sulfo-3H-indol-3-yl)hexanoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

6-(2,3-Dimethyl-5-sulfo-3H-indol-3-yl)hexanoic acid was synthesised as described in Example 5. To a stirred solution of 6-(1-ethyl-2,3-dimethyl-5-sulfo-3H-indol-3-yl)hexanoic acid (1.8 g, 5.3 mmol) in ethanol (200 ml) at ambient temperature was added hydrobromic acid (10 ml 48% aqueous solution). After 1 Hr the reaction solvent was removed in vacuo. The hydrobromide salt was re-dissolved in acetonitrile (150 ml) and acetic acid (1.54 ml) and acrolein diethyl acetal (6.6 g, 51 mmol). The reaction mixture was heated to 70° C. for 30 minutes. The solution was cooled and the solvent removed in vacuum. The product was rapidly purified by preparative HPLC on reverse phase C18 column using gradient elution of water containing 10% acetonitrile to acetonitrile (containing 0.1% TFA) as solvent over 30 minutes. All fractions were monitored by MALDI-TOF mass spectrometry (M/Z=498). Fractions containing product mass were pooled. Evaporation of the solvent gave a sticky mass (162 mg 11%). It was immediately used for the next reaction.

Workup

  1. customAfter 1 Hr the reaction solvent was removed in vacuo
  2. dissolutionThe hydrobromide salt was re-dissolved in acetonitrile (150 ml)
  3. temperatureThe solution was cooled
  4. customthe solvent removed in vacuum
  5. customThe product was rapidly purified by preparative HPLC on reverse phase C18 column
  6. washelution of water containing 10% acetonitrile to acetonitrile (containing 0.1% TFA) as solvent over 30 minutes
  7. additionFractions containing product mass
  8. customEvaporation of the solvent
  9. customgave a sticky mass (162 mg 11%)
  10. customIt was immediately used for the next reaction

Sources & evidence

ORD record
ord-40f61d2258b7461d9a93c6f06f6544e4
Source dataset
uspto-grants-2011_10
Patent number
US08044203B2

Linked notes

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