Dimethylformamide → HCID 57850430, compound

HRID 736670Notes

Reaction equation

HRID 736670 reaction equation
CCN=C=NC[CH2:7][CH2:8][N:9]([CH3:11])[CH3:10].[NH:12]1[CH2:17][CH2:16][CH:15]([CH2:18][CH2:19][OH:20])[CH2:14][CH2:13]1.C(N(CC)CC)C.[S:28](Cl)([C:31]1[CH:37]=[CH:36][C:34]([CH3:35])=[CH:33][CH:32]=1)(=[O:30])=[O:29].CN(C=[O:43])C>CCOC(C)=O.C1COCC1>[CH3:11][N:9]([CH3:10])[CH2:8][C:7]([N:12]1[CH2:17][CH2:16][CH:15]([CH2:18][CH2:19][O:20][S:28]([C:31]2[CH:37]=[CH:36][C:34]([CH3:35])=[CH:33][CH:32]=2)(=[O:30])=[O:29])[CH2:14][CH2:13]1)=[O:43]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 739534-Piperidineethanol

Product 1

HCID 57850430HCID 57850430, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the mixture of N,N-dimethylamino pyridine (1.18 g, 9.66 mmol), EDCI (1.48 g, 7.73 mmol), in DMF (5 mL) was added carboxylic acid (0.398 g, 3.86 mmol), then followed by the addition of 4-piperadinethanol (0.5 g, 3.86 mmol). The reaction mixture was allowed to stir at room temperature for 12 h. The reaction mixture was diluted with EtOAc (75 mL) and washed with brine (60 mL). The EtOAc layer was dried over Na2SO4, filtered, and solvent was evaporated under reduced pressure to afford crude amide. The crude was used for the next tosylation reaction without further purification. To the above crude product (0.827 g, 3.86 mmol), triethyl amine (3.22 mL, 23.18 mmol), in THF (20 mL) was added tosyl chloride (2.21 g, 11.59 mmol) at room temperature and stirred for 12 h. The reaction mixture was concentrated in vacuo and the crude was dissolved in EtOAc (100 mL), washed with sat. aq. NaHCO3 solution (90 mL), followed by brine (90 mL). The EtOAc layer was dried over Na2SO4, filtered, and solvent was evaporated under reduced pressure to afford crude product, which was purified by Isco silica gel flash column using Hexane-EtOAc (1:9) to obtain 0.45 g of toluene-4-sulfonic acid 2-[1-(2-dimethylamino-acetyl)-piperidin-4-yl]-ethyl ester. LC-MS [M+H]+ 369.2

Workup

  1. washwashed with brine (60 mL)
  2. dry with materialThe EtOAc layer was dried over Na2SO4
  3. filtrationfiltered
  4. customsolvent was evaporated under reduced pressure
  5. customto afford crude amide
  6. customThe crude was used for the next tosylation reaction without further purification
  7. stirringstirred for 12 h
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. dissolutionthe crude was dissolved in EtOAc (100 mL)
  10. washwashed with sat. aq. NaHCO3 solution (90 mL)
  11. dry with materialThe EtOAc layer was dried over Na2SO4
  12. filtrationfiltered
  13. customsolvent was evaporated under reduced pressure
  14. customto afford crude product, which
  15. customwas purified by Isco silica gel flash column

Sources & evidence

ORD record
ord-3a01885b4fd6492cb3185a6c38007f99
Source dataset
uspto-grants-2009_09
Patent number
US07595401B2

Reaction notes

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