Propane sultone → 3-[(1r,2s)-2-Methylcyclohexyl]amino-1-propanesulfonic acid

HRID 2219747Notes

Reaction equation

HRID 2219747 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[NH2:8].[CH2:9]1[CH2:15][S:12](=[O:14])(=[O:13])[O:11][CH2:10]1>O1CCCC1>[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][CH2:10][CH2:9][CH2:15][S:12]([OH:14])(=[O:13])=[O:11]

Participants

4

Reactant 2

HCID 14264Propane sultoneHCID 234322-Methylcyclohexylamine

Product 1

HCID 117364843-[(1r,2s)-2-Methylcyclohexyl]amino-1-propanesulfonic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-methylcyclohexylamine (98% cis and trans isomers, 10.0 g, 88.3 mmol) in tetrahydrofuran (60 mL) was slowly added a solution of 1,3-propane sultone (10.5 g, 84.1 mmol) in THF (20 mL). The mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2×50 mL). The solid was dissolved in 50% EtOH/water (200 mL); and solution was treated with Dowex 50WX8 resin (15 g). The suspension stirred at room temperature for 15 min. The resin was removed by filtration. The filtrate was concentrated to half of the original volume on a rotary evaporator. The solid product slowly crystallized. The product was collected by filtration, washed with acetone (2×50 mL) and dried in a vacuum oven (50° C.), to afford compound DJ (10.4 g, 53%): 1H NMR (D2O, 500 MHz) δ ppm 3.15 (m, 1H), 3.03 (m, 1H), 2.88 (t, 2H, J=7.3 Hz), 2.76 (m, 1H), 1.98 (m, 3H), 1.68 (m, 2H), 1.51 (m, 2H), 1.18 (m, 3H), 1.01 (m, 1H), 0.92 (m, 3H). 13C NMR (D2O, 125 MHz) δ ppm 62.97, 48.16, 42.72, 34.77, 33.50, 27.57, 24.51, 24.23, 21.51, 17.80. ES-MS 234 (M-1).

Workup

  1. temperatureat reflux for 2 hours
  2. filtrationThe solid material was collected by filtration
  3. washwashed with acetone (2×50 mL)
  4. dissolutionThe solid was dissolved in 50% EtOH/water (200 mL)
  5. additionand solution was treated with Dowex 50WX8 resin (15 g)
  6. stirringThe suspension stirred at room temperature for 15 min
  7. customThe resin was removed by filtration
  8. concentrationThe filtrate was concentrated to half of the original volume on a rotary evaporator
  9. customThe solid product slowly crystallized
  10. filtrationThe product was collected by filtration
  11. washwashed with acetone (2×50 mL)
  12. customdried in a vacuum oven (50° C.)
  13. customto afford compound DJ (10.4 g, 53%)

Sources & evidence

ORD record
ord-f13ecd0a9df149069b9529ccb59dcc8b
Source dataset
uspto-grants-2008_08
Patent number
US07414076B2

Reaction notes

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