Acetonitrile → HCID 46896895, compound

HRID 551386Notes

Reaction equation

HRID 551386 reaction equation
[Cl:1][C@H:2]1[C@H:6]([CH2:7][CH2:8][CH2:9][C:10]2[S:14][C:13]([C:15]([OH:17])=[O:16])=[CH:12][CH:11]=2)[C@@H:5]([CH2:18][CH2:19][C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=2)[C@H:4]([OH:28])[CH2:3]1.C(=O)(O)[O-].[K+].Br.Br[CH2:36][CH2:37][N:38]([CH2:41][CH3:42])[CH2:39][CH3:40].C(#N)C>O.CCOC(C)=O>[Cl:1][C@H:2]1[C@H:6]([CH2:7][CH2:8][CH2:9][C:10]2[S:14][C:13]([C:15]([O:17][CH2:36][CH2:37][N:38]([CH2:41][CH3:42])[CH2:39][CH3:40])=[O:16])=[CH:12][CH:11]=2)[C@@H:5]([CH2:18][CH2:19][C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=2)[C@H:4]([OH:28])[CH2:3]1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 706072-Bromoethyldiethylammonium bromideHCID 516893Potassium BicarbonateHCID 23653633HCID 23653633, compound

Product 1

HCID 46896895HCID 46896895, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 5-(3-((1R,2R,3R,5R)-5-chloro-2-(3,5-dichlorophenethyl)-3-hydroxycyclopentyl)propyl)thiophene-2-carboxylic acid (212 mg, 0.46 mmol), potassium bicarbonate (212 mg, 2.1 mmol), 2-bromo-N,N-diethylethanamine hydrobromide (132 mg, 0.51 mmol) and acetonitrile (1.5 mL) was heated at 65° C. After 2 d at 65° C., the mixture was cooled to room temperature and diluted with water (50 mL) and EtOAc (100 mL). The phases were separated and the aqueous phase was extracted with EtOAc (2×50 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified on 40 g silica (CH2Cl2→20% MeOH/CH2Cl2, gradient) to afford a mixture of the desired ester and the starting acid. Fractions containing the desired ester were combined and concentrated. The residue was taken up in EtOAc (100 mL) and washed with saturated aqueous NaHCO3 (50 mL). The aqueous phase was extracted with EtOAc (50 mL) and the combined organic phases were dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified on 80 g silica (CH2Cl2→15% MeOH/CH2Cl2, gradient) to afford 103 mg (40%) of 2-(diethylamino)ethyl 5-(3-((1R,2R,3R,5R)-5-chloro-2-(3,5-dichlorophenethyl)-3-hydroxycyclopentyl)propyl)thiophene-2-carboxylate

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with EtOAc (2×50 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified on 40 g silica (CH2Cl2→20% MeOH/CH2Cl2, gradient)
  8. customto afford
  9. concentrationconcentrated
  10. washwashed with saturated aqueous NaHCO3 (50 mL)
  11. extractionThe aqueous phase was extracted with EtOAc (50 mL)
  12. dry with materialthe combined organic phases were dried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe crude residue was purified on 80 g silica (CH2Cl2→15% MeOH/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-80370c2049854502b1337a85ea9ed838
Source dataset
uspto-grants-2011_05
Patent number
US07947732B2

Reaction notes

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