1,2-Dichloroethane → HCID 21883458, compound

HRID 722173Notes

Reaction equation

HRID 722173 reaction equation
Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH:4]([CH2:10][C:11]([OH:13])=O)[CH2:3]2.FC1C(O)=C(F)C(F)=C(F)C=1F.C(Cl)C[Cl:28].[Br:30][C:31]1[CH:32]=[C:33]([CH:35]=[CH:36][CH:37]=1)[NH2:34].C(=O)(O)[O-].[Na+]>ClCCl.C(OCC)(=O)C.CN(C=O)C>[ClH:28].[N:2]12[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9]1)[CH:4]([CH2:10][C:11]([NH:34][C:33]1[CH:35]=[CH:36][CH:37]=[C:31]([Br:30])[CH:32]=1)=[O:13])[CH2:3]2

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 115623-BromoanilineHCID 13041PentafluorophenolHCID 516892Sodium BicarbonateHCID 230241472-(Quinuclidin-3-yl)acetic acid hydrochloride

Product 1

HCID 21883458HCID 21883458, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

500 mg (2.34 mmol) of 1-azabicyclo[2.2.2]oct-3-ylacetic acid hydrochloride are suspended in 10 ml of dichloromethane and cooled to 0° C. 1.79 g (9.72 mmol) of pentafluorophenol and 699.0 mg (3.65 mmol) of EDC are added, and the mixture is stirred at room temperature overnight. The residue after concentration in vacuo is mixed with 8 ml of DMF and 627.3 mg (3.56 mmol) of 3-bromoaniline and left to stir at room temperature for a further night. The reaction mixture is stirred with 10 ml of 10% strength aqueous sodium bicarbonate solution and 10 ml of ethyl acetate. After the resulting precipitate has been filtered off with suction and washed with ethyl acetate, the two-phase filtrate is separated and the aqueous phase is extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated. The crude mixture is purified by preparative HPLC. The product fractions are concentrated, taken up in a 5:1 mixture of methanol and 1M hydrochloric acid and again concentrated. Drying under high vacuum results in 600 mg (57.3% of theory) of the title compound, which is employed without further purification in the following stages.

Workup

  1. concentrationThe residue after concentration in vacuo
  2. waitleft
  3. stirringto stir at room temperature for a further night
  4. filtrationAfter the resulting precipitate has been filtered off with suction
  5. washwashed with ethyl acetate
  6. customthe two-phase filtrate is separated
  7. extractionthe aqueous phase is extracted three times with ethyl acetate
  8. dry with materialThe combined organic phases are dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe crude mixture is purified by preparative HPLC
  11. concentrationThe product fractions are concentrated
  12. additiontaken up in a 5:1 mixture of methanol and 1M hydrochloric acid
  13. concentrationagain concentrated
  14. customDrying under high vacuum

Sources & evidence

ORD record
ord-8b41af7c1811471891b293570a08faa7
Source dataset
uspto-grants-2006_11
Patent number
US07138410B2

Reaction notes

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