Hydrochloric Acid → 4-[3-[ethyl[3-(propylthio)propyl]amino]-2(R)-hydroxypropoxy]benzonitrile

HRID 466223Notes

Reaction equation

HRID 466223 reaction equation
[C:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][CH2:8][C@H:9]([OH:16])[CH2:10]OS(C)(=O)=O)=[CH:5][CH:4]=1)#[N:2].[CH2:19]([NH:21][CH2:22][CH2:23][CH2:24][S:25][CH2:26][CH2:27][CH3:28])[CH3:20].C(=O)([O-])[O-].[K+].[K+].Cl>CO.CO.ClCCl.CCOCC.C(#N)C>[CH2:19]([N:21]([CH2:22][CH2:23][CH2:24][S:25][CH2:26][CH2:27][CH3:28])[CH2:10][C@@H:9]([OH:16])[CH2:8][O:7][C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:18][CH:17]=1)[CH3:20]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 15066864(2S)-1-(4-cyanophenoxy)-3-methane-sulfonyloxypropan-2-olHCID 15066865Ethyl (3-propylthio)propylamine

Product 1

HCID 150668444-[3-[ethyl[3-(propylthio)propyl]amino]-2(R)-hydroxypropoxy]benzonitrileYield 71%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

11.7 g of (2S)-1-(4-cyanophenoxy)-3-methanesulfonyloxy propane-2-ol, was stirred and refluxed overnight with ethyl (3-propylthio)propylamine (13.9 g), potassium carbonate (12.6 g) and acetonitrile (100 ml). Filtration and evaporation gave 21.5 g of crude product which was distributed between ether and 2 M hydrochloric acid. The aqueous layer was extracted three times with dichloromethane, in which it was present as an ion pair. Evaporation and distribution between ether and 1 M sodium hydroxide yielded the free base in the ether layer. Chromatography over silica using methanol-dichloromethane 5:95 as mobile phase gave 10.3 g of the title compound as a colourless oil, [α]D20 -24,2° (c 1.0, CH3OH).

Workup

  1. filtrationFiltration and evaporation
  2. customgave 21.5 g of crude product which
  3. extractionThe aqueous layer was extracted three times with dichloromethane
  4. customEvaporation and distribution between ether and 1 M sodium hydroxide
  5. customyielded the free base in the ether layer

Sources & evidence

ORD record
ord-7661230b9c2945c095e1fcfb5308fa12
Source dataset
uspto-grants-1992_10
Patent number
US05155133

Reaction notes

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