Triethylamine → HCID 54110030, compound

HRID 2187452Notes

Reaction equation

HRID 2187452 reaction equation
C([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8]([OH:10])=O)(=O)C.[NH2:14][C@@H:15]1[CH2:24][CH2:23][C:22]2[C:17](=[C:18]([N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)[CH:19]=[CH:20][CH:21]=2)[CH2:16]1.C(N(CC)CC)C>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:31][N:28]1[CH2:29][CH2:30][N:25]([C:18]2[CH:19]=[CH:20][CH:21]=[C:22]3[C:17]=2[CH2:16][C@H:15]([NH:14][C:8](=[O:10])[C:7]2[CH:11]=[CH:12][CH:13]=[C:5]([OH:4])[CH:6]=2)[CH2:24][CH2:23]3)[CH2:26][CH2:27]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 2386693-Acetoxybenzoic acidHCID 53960413(R)-2-amino-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalene

Product 1

HCID 54110030HCID 54110030, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 3-acetoxybenzoic acid (130 g, 0.69 mol) in thionyl chloride (400 mL) was stirred at ambient temperature for 4 days. 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 (100 mg, 0.52 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 (120 mg, 0.50 mmol) and triethylamine (100 μL, 0.75 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 dilute 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 (25 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 methylene chloride. 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: 93 mg (51%) of the title compound as white crystals: mp 117° C. decomp, [α]21D −10° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 365 (22, M+).

Workup

  1. customThe excess of thionyl chloride was evaporated in vacuo
  2. additionthe residue was treated with toluene
  3. customagain the solvent was removed in vacuo
  4. additionAfter the addition
  5. washwas then washed with dilute aqueous sodium hydrogen carbonate
  6. customThe phases were separated
  7. dry with materialthe organic phase was dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. dissolutionThe residue was dissolved in 99.5% ethanol (25 mL)
  11. additionconcentrated hydrochloric acid (5 mL) was added
  12. waitAfter 17 h
  13. customthe solvent evaporated in vacuo
  14. customThe residue was partitioned between water and methylene chloride
  15. customThe organic phase was separated
  16. dry with materialdried (Na2SO4)
  17. filtrationfiltered
  18. customevaporated in vacuo

Sources & evidence

ORD record
ord-6fe9fbcb88ee49d1aac98d7361e4b7d1
Source dataset
uspto-grants-2002_06
Patent number
US06410530B1

Reaction notes

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