Triethylamine → HCID 53997359, compound

HRID 1954800Notes

Reaction equation

HRID 1954800 reaction equation
C([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([O-:11])=O)=[CH:7][CH:6]=1)(=O)C.[Na+].[NH2:15][C@@H:16]1[CH2:25][CH2:24][C:23]2[C:18](=[C:19]([N:26]3[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)[CH:20]=[CH:21][CH:22]=2)[CH2:17]1.C(N(CC)CC)C>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:32][N:29]1[CH2:30][CH2:31][N:26]([C:19]2[CH:20]=[CH:21][CH:22]=[C:23]3[C:18]=2[CH2:17][C@H:16]([NH:15][C:9](=[O:11])[C:8]2[CH:7]=[CH:6][C:5]([OH:4])=[CH:13][CH:12]=2)[CH2:25][CH2:24]3)[CH2:27][CH2:28]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 23709606HCID 23709606, compoundHCID 53960413(R)-2-amino-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalene

Product 1

HCID 53997359HCID 53997359, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

A suspension of sodium 4-acetoxybenzoate (1.0 g, 5.4 mmol) in thionyl chloride (15 mL) was heated at reflux for I h (the mixture became homogeneous). The excess of thionyl chloride was evaporated in vacuo, the residue was treated with toluene and again the solvent was removed in vacuo. Crude acid chloride (150 mg, 0.77 mmol ) was dissolved in methylene chloride (5 mL) and added dropwise to an ice-cooled solution of (R)-2-amino-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalene (180 mg, 0.73 mmol) and triethylamine (150 μL, 1.1 mmol) in methylene chloride (20 mL). After the addition the reaction was allowed to stir at ambient temperature for 15 min and was then washed with diluted aqueous sodium hydrogen carbonate. The phases were separated and the organic phase was dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in 99.5% ethanol (15 mL) and concentrated hydrochloric acid (5 mL) was added. After 17 h, the pH was adjusted to 8 and the solvent evaporated in vacuo. The residue was partitioned between water and chloroform. The organic phase was separated, dried (Na2SO4), filtered and evaporated in vacuo to give a crude product which was purified on a silica gel column using chloroform/ethanol saturated with NH3 (100:4) as the eluent. Yield: 70 mg (26%) of the title compound as an oil: [α]21D -17° (c 0.50, chloroform); EIMS (70 eV) m/z (relative intensity) 365 (24, M+).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for I h (the mixture
  3. customThe excess of thionyl chloride was evaporated in vacuo
  4. additionthe residue was treated with toluene
  5. customagain the solvent was removed in vacuo
  6. additionAfter the addition the reaction
  7. washwas then washed with diluted aqueous sodium hydrogen carbonate
  8. customThe phases were separated
  9. dry with materialthe organic phase was dried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. dissolutionThe residue was dissolved in 99.5% ethanol (15 mL)
  13. additionconcentrated hydrochloric acid (5 mL) was added
  14. waitAfter 17 h
  15. customthe solvent evaporated in vacuo
  16. customThe residue was partitioned between water and chloroform
  17. customThe organic phase was separated
  18. dry with materialdried (Na2SO4)
  19. filtrationfiltered
  20. customevaporated in vacuo

Sources & evidence

ORD record
ord-b8ecffe0ffb44bca87373b05c76f63b3
Source dataset
uspto-grants-2000_09
Patent number
US06124283

Reaction notes

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