Potassium Carbonate → (3R)-N-(4'-Nitrobiphenyl-4-yl)quinuclidine-3-carboxamide hydrochloride

HRID 1661141Notes

Reaction equation

HRID 1661141 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl.[N:8]12[CH2:15][CH2:14][CH:11]([CH2:12][CH2:13]1)[C@@H:10]([C:16]([Cl:18])=[O:17])[CH2:9]2.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=2)=[CH:22][CH:21]=1.O1CCOCC1>CN(C=O)C>[ClH:18].[N+:32]([C:29]1[CH:28]=[CH:27][C:26]([C:23]2[CH:24]=[CH:25][C:20]([NH:19][C:16]([C@@H:10]3[CH:11]4[CH2:14][CH2:15][N:8]([CH2:13][CH2:12]4)[CH2:9]3)=[O:17])=[CH:21][CH:22]=2)=[CH:31][CH:30]=1)([O-:34])=[O:33]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 145934-Amino-4'-nitrobiphenylHCID 312751,4-DioxaneHCID 57462844(3R)-Quinuclidine-3-carbonyl chloride hydrochloride

Product 1

HCID 67427704(3R)-N-(4'-Nitrobiphenyl-4-yl)quinuclidine-3-carboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

480 mg (3.50 mmol) of potassium carbonate are added to a mixture, prepared under argon, of 490 mg (2.33 mmol) of (3R)-quinuclidine-3-carbonyl chloride hydrochloride (Example 5A) and 250 mg (1.17 mmol) of 4-amino-4′-nitrobiphenyl in 11 ml of a 10:1 mixture of dioxane and DMF. The reaction mixture is stirred at 100° C. for 18 h and then concentrated. The residue is suspended in methanol and filtered. The filtration residue is washed with water, mixed with 20 ml of a 3:1 mixture of acetonitrile and 1 N hydrochloric acid, again concentrated and dried under high vacuum. The above filtrate is purified by preparative HPLC. The product fractions are concentrated, taken up in 5 ml of a 3:1 mixture of acetonitrile and 1 N hydrochloric acid, again concentrated and dried under high vacuum. 291 mg (61.7% of theory) of the title compound are obtained from the filtration residue, and a further 65 mg (12.4% of theory) are obtained from the filtrate, in this way.

Workup

  1. concentrationconcentrated
  2. filtrationfiltered
  3. washThe filtration residue is washed with water
  4. additionmixed with 20 ml of a 3:1 mixture of acetonitrile and 1 N hydrochloric acid
  5. concentrationagain concentrated
  6. customdried under high vacuum
  7. customThe above filtrate is purified by preparative HPLC
  8. concentrationThe product fractions are concentrated
  9. additiontaken up in 5 ml of a 3:1 mixture of acetonitrile and 1 N hydrochloric acid
  10. concentrationagain concentrated
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-9a07a1be06484c339dbdb291ad6d3eb0
Source dataset
uspto-grants-2011_10
Patent number
US08030329B2

Reaction notes

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