Phosphoric Acid → HCID 68816006, compound

HRID 730573Notes

Reaction equation

HRID 730573 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[C:16](Br)=[CH:17][N:18]3[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].P(=O)(O)(O)O.[OH-].[Na+].CCOCC>COCCO>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH2:16][CH2:17][N:18]3[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 1004Phosphoric AcidHCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 57834978HCID 57834978, compound

Product 1

HCID 68816006HCID 68816006, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
140 °C

Procedure

4-[3-Bromo-1-(3-fluoro-benzyl)-1H-indol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (273 mg) was dissolved in 3 mL of 2-methoxyethanol and 85% phosphoric acid (575 mL) was added. The dark solution was heated to 140° C. and stirred for 16 h. The next day the mixture was made basic with 1.0 N NaOH and Et2O was added. The organic layer was separated, washed with brine, and dried over sodium sulfate. After filtering and removing solvent the crude material was taken up in 3 mL of THF and di-tert-butyldicarbonate (218 mg) was added. The mixture was stirred for 24 hours at room temperature, after which the mixture was partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The resulting residue was purified by column chromatography to provide 115 mg of 4-[1-(3-fluoro-benzyl)-2,3-dihydro-1H-indol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester, MS: 326 (M−Boc+H)+.

Workup

  1. additionwas added
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationAfter filtering
  6. customremoving solvent the crude material
  7. additiondi-tert-butyldicarbonate (218 mg) was added
  8. stirringThe mixture was stirred for 24 hours at room temperature
  9. customafter which the mixture was partitioned between water and ethyl acetate
  10. dry with materialThe organic layer was dried over sodium sulfate
  11. customevaporated under reduced pressure
  12. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-491c00d29fc943338b3a06052e4d1a62
Source dataset
uspto-grants-2009_09
Patent number
US07582760B2

Reaction notes

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