Water → HCID 22873798, compound

HRID 1683872Notes

Reaction equation

HRID 1683872 reaction equation
Cl.[CH2:2]([S:4]([CH2:7][CH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH2:18][C@H:19]1[CH2:23][CH2:22][CH2:21][NH:20]1)(=[O:6])=[O:5])[CH3:3].C(N(CC)CC)C.[CH2:31]1[O:34][C@H:32]1[CH3:33].O>CO>[CH2:2]([S:4]([CH2:7][CH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH2:18][C@H:19]1[CH2:23][CH2:22][CH2:21][N:20]1[CH2:31][C@@H:32]([OH:34])[CH3:33])(=[O:6])=[O:5])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 146262(2S)-2-MethyloxiraneHCID 22873789HCID 22873789, compound

Product 1

HCID 22873798HCID 22873798, compoundYield 22.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 5-(2-ethylsulphonylethyl)-3-(2(R)-pyrrolidinylmethyl)-1H-indole hydrochloride (Preparation 5; 200 mg, 0.56 mmol) in methanol (2 ml) at room temperature under nitrogen was added triethylamine (0.09 ml). After 10 minutes, (S)-(-)-propylene oxide (0.05 ml, 0.71 mmol) and then water (12 ml) were added and the reaction mixture was warmed at 50° C. for 18 hours. The cool reaction mixture was evaporated under reduced pressure and the residue partitioned between ethyl acetate and water. The organic phase was separated, washed with water, dried (Na2SO4) and evaporated under reduced pressure to give an oil. Purification by column chromatography on silica gel, eluting with a gradient of ethanol in dichloromethane (0 to 10% ethanol), afforded the title compound as a gum (48 mg). Rf 0.50 (SS 4). [α]D25 +58° (c=0.1, CH3OH). Found: C,57.44; H,7.58; N,6.39. C20H30N2O3S; 0.50 H2O; 0.50 CH2Cl2 requires C,57.26; H,7.50; N,6.52%. δ(CDCl3): 1.15(3H,d), 1.38(3H,t), 1.50-1.90(4H,m), 2.20-2.38(2H,m), 2.60-2.75(2H,m), 2.85-2.95(3H,m), 3.10(1H,m), 3.20-3.38(5H,m), 3.60-3.90(2H,m), 5.30(1H,s,CH2Cl2), 7.02(1H,d), 7.05(1H,s), 7.32(1H,d), 7.40(1H,s), 8.10(1H,br s).

Workup

  1. customThe cool reaction mixture
  2. customwas evaporated under reduced pressure
  3. customthe residue partitioned between ethyl acetate and water
  4. customThe organic phase was separated
  5. washwashed with water
  6. dry with materialdried (Na2SO4)
  7. customevaporated under reduced pressure
  8. customto give an oil
  9. customPurification by column chromatography on silica gel
  10. washeluting with a gradient of ethanol in dichloromethane (0 to 10% ethanol)

Sources & evidence

ORD record
ord-f80b1dd266f348d1869eb32f923627c6
Source dataset
uspto-grants-1997_06
Patent number
US05639779

Reaction notes

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