Propane sultone → 1-Propanesulfonic acid, 3-[(1-ethynylcyclohexyl)amino]-

HRID 239755Notes

Reaction equation

HRID 239755 reaction equation
[C:1]([C:3]1([NH2:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)#[CH:2].[CH2:10]1[CH2:16][S:13](=[O:15])(=[O:14])[O:12][CH2:11]1>C1COCC1>[C:1]([C:3]1([NH:9][CH2:11][CH2:10][CH2:16][S:13]([OH:15])(=[O:14])=[O:12])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)#[CH:2]

Participants

4

Reactant 2

HCID 14264Propane sultoneHCID 1216911-Ethynylcyclohexylamine

Product 1

HCID 118174291-Propanesulfonic acid, 3-[(1-ethynylcyclohexyl)amino]-Yield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-ethynylcyclohexylamine (6 g, 48.7 mmol) and 1,3-propane sultone (6.55 g, 53.6 mmol) in THF (35 mL) was heated at reflux for 2 hours (thick paste). The mixture was cooled to room temperature. The solid was collected by filtration, rinsed with THF (3×5 mL), air-dried 15 minutes (7.3 g). The solid was suspended in ethanol (30 mL) and the suspension was heated at reflux for 1 hour. The mixture was then cooled to room temperature and the solid was collected by suction filtration, rinsed with ethanol (2×5 mL), air-dried for 10 min, and further dried in a vacuum oven at 60° C. overnight (crop1, 7.10 g). The combined mother liquors were stirred overnight at room temperature. There was a lot of solid. The solid was collected by filtration, rinsed with acetone (3×5 mL), air-dried for 30 minutes, and then suspended in ethanol (12 mL). The suspension was heated at reflux for 1 hour. The mixture was then cooled to room temperature and the solid was collected by suction filtration, rinsed with ethanol (2×5 mL), air-dried for 2 minutes, and further dried in a vacuum oven at 60° C. overnight (crop 2: 1.85 g). Compound DX was obtained as a fine white solid (two crops in total 8.95 g, 75% yield). 1H NMR (500 MHz, D2O) δ 0.95-1.05 (m, 1H), 1.38-1.54 (m, 5H), 1.60-1.64 (m, 2H), 1.94 (qt, J=7.8 Hz, 2H), 2.85 (t, J=7.3 Hz, 2H), 3.01 (s, 1H), 3.22 (t, J=7.8 Hz, 2H). 13C NMR (125 MHz, D2O) δ 21.8, 22.3, 24.2, 34.4, 40.9, 48.0, 59.2, 78.6, 79.3. ES-MS 243.0 (M−1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours (thick paste)
  3. filtrationThe solid was collected by filtration
  4. washrinsed with THF (3×5 mL)
  5. customair-dried 15 minutes (7.3 g)
  6. temperaturethe suspension was heated
  7. temperatureat reflux for 1 hour
  8. temperatureThe mixture was then cooled to room temperature
  9. filtrationthe solid was collected by suction filtration
  10. washrinsed with ethanol (2×5 mL)
  11. customair-dried for 10 min
  12. customfurther dried in a vacuum oven at 60° C. overnight (crop1, 7.10 g)
  13. filtrationThe solid was collected by filtration
  14. washrinsed with acetone (3×5 mL)
  15. customair-dried for 30 minutes
  16. temperatureThe suspension was heated
  17. temperatureat reflux for 1 hour
  18. temperatureThe mixture was then cooled to room temperature
  19. filtrationthe solid was collected by suction filtration
  20. washrinsed with ethanol (2×5 mL)
  21. customair-dried for 2 minutes
  22. customfurther dried in a vacuum oven at 60° C. overnight (crop 2: 1.85 g)
  23. customCompound DX was obtained as a fine white solid (two crops in total 8.95 g, 75% yield)

Sources & evidence

ORD record
ord-97720175e0cb4dcf8422174659c9fca0
Source dataset
uspto-grants-2014_02
Patent number
US08642801B2

Reaction notes

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