Chloroacetonitrile → Descarboxymethyl Cyanomethyl Treprostinil

HRID 245601

Reaction equation

HRID 245601 reaction equation
[OH:1][C@@H:2]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:3][CH2:4][C@@H:5]1[C@H:9]2[CH2:10][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([OH:18])[C:16]=3[CH2:17][C@H:8]2[CH2:7][C@H:6]1[OH:19].C([O-])([O-])=O.[K+].[K+].Cl[CH2:32][C:33]#[N:34]>CC(C)=O>[OH:19][C@H:6]1[C@H:5]([CH2:4][CH2:3][C@@H:2]([OH:1])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C@H:9]2[CH2:10][C:11]3[C:16]([CH2:17][C@H:8]2[CH2:7]1)=[C:15]([O:18][CH2:32][C:33]#[N:34])[CH:14]=[CH:13][CH:12]=3

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 11430Potassium CarbonateHCID 11174966Descarboxymethyl treprostinil

Product 1

HCID 11314741Descarboxymethyl Cyanomethyl TreprostinilYield 82%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
30 °C

Procedure

(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-1-((S)-3-hydroxyoctyl)-1H-cyclopenta[b]naphthalene-2,5-diol (2 g, 0.005 mol) in dry acetone (20 ml) was treated with K2CO3 (2.07 g, 0.015 mol), chloroacetonitrile (0.64 ml, 0.010 mol) and tetrabutylbromide (0.32 g, 0.001 mmol). The mixture was heated at 30° C. overnight. Then, the reaction mixture was filtered with celite pad. The filtrate was evaporated off under vacuum. The crude product was purified by chromatography on silica gel using a mixture of hexane and ethyl acetate as a gradient eluent. Yield: 82%

Workup

  1. filtrationThen, the reaction mixture was filtered with celite pad
  2. customThe filtrate was evaporated off under vacuum
  3. customThe crude product was purified by chromatography on silica gel using
  4. additiona mixture of hexane and ethyl acetate as a gradient eluent

Sources & evidence

ORD record
ord-bb79e61ee673448a99e72fa55b42804e
Source dataset
uspto-grants-2014_02
Patent number
US08658837B2

Linked notes

Loading…