Hydrochloric Acid → 1-tert-Butoxycarbonylmethyl-6-methoxy-1H-indole-3-carboxylic acid

HRID 1527207Notes

Reaction equation

HRID 1527207 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:12]([OH:14])=[O:13])=[CH:8][NH:9]2)=[CH:5][CH:4]=1.[H-].[Na+].[C:17]([O:21][C:22](=[O:25])[CH2:23]Br)([CH3:20])([CH3:19])[CH3:18].[NH4+].[Cl-].Cl>CN(C=O)C>[C:17]([O:21][C:22]([CH2:23][N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:11]=2)[C:7]([C:12]([OH:14])=[O:13])=[CH:8]1)=[O:25])([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 79177tert-Butyl bromoacetateHCID 177509566-Methoxy-1H-indole-3-carboxylic acid

Product 1

HCID 682834641-tert-Butoxycarbonylmethyl-6-methoxy-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled suspension of 6-methoxy-1H-indole-3-carboxylic acid (1 g, 5.23 mmol) in DMF (35 mL) was added NaH (60% suspension in oil; 0.523 g, 13.1 mmol) in one portion, and the mixture was stirred at 0° C. for 30 min. Tert-butyl-2-bromoacetate (0.85 mL, 5.75 mmol) was then added dropwise, and stirring was continues at RT overnight. The reaction mixture was neutralized by addition of saturated NH4Cl, and the solution was then adjusted to pH=2-3 by addition of 0.1N HCl. The aqueous layer was repeatedly extracted with CH2Cl2, the combined organics were washed with brine, dried (phase separator) and concentrated in vacuo. The residue was dissolved in a small volume of methanol, followed by addition of water until a solid precipitated. The precipitate was filtered off, washed with water and dried in vacuo to afford the title compound as a white solid. MS (LC/MS): 306 [M+H]+, 328 [M+Na]+; tR (HPLC conditions c): 4.67 min.

Workup

  1. stirringstirring
  2. waitwas continues at RT overnight
  3. extractionThe aqueous layer was repeatedly extracted with CH2Cl2
  4. washthe combined organics were washed with brine
  5. customdried (phase separator)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in a small volume of methanol
  8. additionfollowed by addition of water until a solid
  9. customprecipitated
  10. filtrationThe precipitate was filtered off
  11. washwashed with water
  12. customdried in vacuo

Sources & evidence

ORD record
ord-3d6e7ffe48cb4f5a9604760818abbb59
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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