Hexylamine → HCID 178444719, compound

HRID 2410049Notes

Reaction equation

HRID 2410049 reaction equation
[CH:1]1([N:7]=[C:8]=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:10]([NH2:16])[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].[C:17](Cl)(=[O:22])[CH2:18][C:19](Cl)=[O:20].C(N(C(C)C)CC)(C)C.[N:33]([CH2:36][C:37]([O:39]CC)=[O:38])=[C:34]=[O:35]>ClCCl>[CH:1]1([N:7]2[C:19]([OH:20])=[C:18]([C:34]([NH:33][CH2:36][C:37]([OH:39])=[O:38])=[O:35])[C:17](=[O:22])[N:16]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:8]2=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 8102HexylamineHCID 18502Cyclohexyl isocyanateHCID 74269Propanedioyl dichlorideHCID 76283Ethyl isocyanatoacetateHCID 81531Diisopropylethylamine

Product 1

HCID 178444719HCID 178444719, compoundYield 24.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cyclohexyl isocyanate (635 uL, 5.0 mmoles) was added to a solution of n-hexylamine (660 uL, 5.0 mmoles) in dichloromethane (100 mL) and the mixture stirred for 1 hour. Malonyl dichloride (486 uL, 5.0 mmoles) was added and the mixture was heated to gentle reflux for 1 hour. The mixture was washed with 1 molar hydrochloric acid (×2), dried and evaporated. The residue was redissolved in dichloromethane (50 mL) and diisopropylethylamine (1.73 mL, 10 mmoles) and the mixture was treated with ethyl isocyanatoacetate (561 uL, 5.0 mmoles). After stirring overnight the mixture was washed with 1 molar hydrochloric acid, dried and evaporated. The residue was dissolved in ethanol (5 mL) and treated with 6 molar sodium hydroxide (2.0 mL). The mixture was stirred for 1 hour, acidified and extracted into ethyl acetate. The organic solution was washed with 1 molar hydrochloric acid, dried and evaporated to a brown oil. The crude material was stood in a freezer overnight in hexane to afford some solid. The liquors were concentrated and purified by preparative HPLC (acetonitrile-water-0.1% TFA) to give additional material which was combined with the previously obtained solid and recrystallized from ethanol-water to give the title compound (480 mg, 24%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.09 (br. s., 1 H), 10.15 (t, J=5.56 Hz, 1 H), 4.53-4.73 (m, 1 H), 4.05-4.18 (m, 2 H), 3.78 (t, 2 H), 2.16-2.36 (m, 2 H), 1.79 (d, J=12.38 Hz, 2 H), 1.42-1.71 (m, 5 H), 1.26 (s, 8 H), 1.03-1.19 (m, 1 H), 0.79-0.92 (m, 3 H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto gentle reflux for 1 hour
  3. washThe mixture was washed with 1 molar hydrochloric acid (×2)
  4. customdried
  5. customevaporated
  6. dissolutionThe residue was redissolved in dichloromethane (50 mL)
  7. stirringAfter stirring overnight the mixture
  8. washwas washed with 1 molar hydrochloric acid
  9. customdried
  10. customevaporated
  11. dissolutionThe residue was dissolved in ethanol (5 mL)
  12. additiontreated with 6 molar sodium hydroxide (2.0 mL)
  13. stirringThe mixture was stirred for 1 hour
  14. extractionextracted into ethyl acetate
  15. washThe organic solution was washed with 1 molar hydrochloric acid
  16. customdried
  17. customevaporated to a brown oil
  18. waitThe crude material was stood in a freezer overnight in hexane
  19. customto afford some solid
  20. concentrationThe liquors were concentrated
  21. custompurified by preparative HPLC (acetonitrile-water-0.1% TFA)
  22. customto give additional material which
  23. customrecrystallized from ethanol-water

Sources & evidence

ORD record
ord-015d023f9c794aa8b80cb1b7b9e14853
Source dataset
uspto-grants-2014_08
Patent number
US08815884B2

Reaction notes

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