Ethylenediamine → (2S)-2-Ethyl-1-thia-4,8-diazaspiro[4.5]decan-3-one

HRID 1825846Notes

Reaction equation

HRID 1825846 reaction equation
[CH3:1][CH2:2][C@@H:3]1[S:8][C:7]2([CH2:13][CH2:12][N:11](C)[CH2:10][CH2:9]2)[NH:6][C:4]1=[O:5].ClC1C=CC=C(C(OO)=O)C=1.C(N)CN.[OH-].[Na+]>ClCCl.[Fe](Cl)Cl>[CH2:2]([C@H:3]1[C:4](=[O:5])[NH:6][C:7]2([CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[S:8]1)[CH3:1]

Participants

7

Reactant 4

HCID 3301EthylenediamineHCID 14798Sodium HydroxideHCID 70297m-Chloroperbenzoic acid2×HCID 10013505AF 267B

Product 1

HCID 9794221(2S)-2-Ethyl-1-thia-4,8-diazaspiro[4.5]decan-3-one

Reagents, catalysts & solvents 2

HCID 24458Ferrous ChlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

To a cooled (ice-salt bath) stirred solution of AF267B (6.1 gr, 0.028 mol) in dichloromethane (60 ml) was added m-chloroperbenzoic acid (mCPBA) in small portions over a period of 15 min mCPBA (70%, 7.02 gr, 0.028 mol total). The mixture was stirred for 1 hr and then treated with iron (II) chloride (2.14 ml of 1M solution in water). Stirring and cooling (−10° C.) were continued for 1 hr and then stirring continued for 2 hrs at room temperature. Ethylene diamine (1.9 ml, 0.285 mol), sodium hydroxide (30.5 ml of 2N aqueous solution), and petroleum ether 40–60° C. (60 ml) were added. After vigorous shaking the layers were separated, the aqueous layer was extracted with mixture of dichloromethane/petroleum ether 1:1 (600 ml) followed by dichloromethane (first 600 ml then 300 ml). The combined extracts were dried (Na2SO4), filtered and the solvents were removed under reduced pressure. Flash chromatography (silica-gel 60, 230–400 mesh, Merck 1.09385, elution with methanol/chloroform/ammonium hydroxide 10:89:1 v/v) of the residue gave AF292. 1H NMR (CDCl3) δ 1.02 (t, j=7 Hz, 3H), 1.76 1.92 and 2.07 (3×m, 6H), 2.84 (m, 2H), 3.04 (m, 2H), 3.83 (dd, j=8.8,4 Hz, 1H), 7.66 (NH) ppm; 13C NMR (CDCl3) δ 11.50, 44.10, 48.80, 64.22, 175.22 ppm: MS m/e 200(M+). The compound was >99.9% purity by HPLC, GC.

Workup

  1. stirringStirring
  2. waitwere continued for 1 hr
  3. stirringstirring
  4. waitcontinued for 2 hrs at room temperature
  5. stirringAfter vigorous shaking the layers
  6. customwere separated
  7. extractionthe aqueous layer was extracted with mixture of dichloromethane/petroleum ether 1:1 (600 ml)
  8. dry with materialThe combined extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. customthe solvents were removed under reduced pressure
  11. washFlash chromatography (silica-gel 60, 230–400 mesh, Merck 1.09385, elution with methanol/chloroform/ammonium hydroxide 10:89:1 v/v) of the residue
  12. customgave AF292

Sources & evidence

ORD record
ord-7781844c27ed429eac2cf767e2d8c0da
Source dataset
uspto-grants-2006_05
Patent number
US07049321B2

Reaction notes

Loading…