1,1'-Carbonyldiimidazole → HCID 67875977, compound

HRID 2254619Notes

Reaction equation

HRID 2254619 reaction equation
N[C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([I:20])[CH:15]=2)[CH:3]=1.C(N1C=CN=C1)([N:23]1C=CN=C1)=O.[NH2:33][C@H:34]1[CH:39]2[CH2:40][CH2:41][N:36]([CH2:37][CH2:38]2)[CH2:35]1>O1CCCC1.CN(C)C=O>[NH2:23][C:3]1[C:4]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([I:20])[CH:15]=2)=[C:5]([CH:9]=[C:10]([Cl:11])[CH:2]=1)[C:6]([NH:33][C@H:34]1[CH:39]2[CH2:40][CH2:41][N:36]([CH2:37][CH2:38]2)[CH2:35]1)=[O:8]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 719216(S)-quinuclidin-3-amineHCID 19742819HCID 19742819, compound

Product 1

HCID 67875977HCID 67875977, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-amino-5-chloro-2-[(3-iodophenyl)methoxy]benzoic acid (3.23 g, 8.0 mmol) in anhydrous tetrahydrofuran (4 mL) and anhydrous N,N-dimethylformamide (4 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.46 g, 9.9 mmol), stirred for 45 minutes, and degased over 15 minutes under a stream of nitrogen. A solution of (S)-3-aminoquinuclidine (1.54 g, 12.2 mmol) in anhydrous tetrahydrofuran (4 mL) was added, and the mixture was stirred at room temperature for 18 hours, warmed to 55°±5° C. for three hours, and concentrated in vacuo. The residue was partitioned between 3.0N sodium hydroxide (50 mL) and toluene (100 mL) containing some 2-propanol, and the organic layer was separated. The aqueous solution was extracted with toluene (50 mL) containing some 2-propanol, and the combined organic solution was concentrated in vacuo. The residue was washed with water to remove most of the imidazole, then dried azeotropically with toluene, taken up in tetrahydrofuran, and filtered through a short column of alumina (eluted with 10% methanol/tetrahydrofuran). The filtrate was concentrated in vacuo, taken up in warm acetone, and filtered. After a few hours, a solid had crystallized, and this was collected and dried in vacuo to afford (following second crop) 1.10 g (27%) of colorless solid; mp 101.5°-104° C., [α]D22 -6.35° (C=1 in methanol).

Workup

  1. customdegased over 15 minutes under a stream of nitrogen
  2. stirringthe mixture was stirred at room temperature for 18 hours
  3. temperaturewarmed to 55°±5° C. for three hours
  4. concentrationconcentrated in vacuo
  5. customThe residue was partitioned between 3.0N sodium hydroxide (50 mL) and toluene (100 mL)
  6. additioncontaining some 2-propanol
  7. customthe organic layer was separated
  8. extractionThe aqueous solution was extracted with toluene (50 mL)
  9. additioncontaining some 2-propanol
  10. concentrationthe combined organic solution was concentrated in vacuo
  11. washThe residue was washed with water
  12. customto remove most of the imidazole
  13. dry with materialdried azeotropically with toluene
  14. filtrationfiltered through a short column of alumina (eluted with 10% methanol/tetrahydrofuran)
  15. concentrationThe filtrate was concentrated in vacuo
  16. filtrationfiltered
  17. waitAfter a few hours
  18. customa solid had crystallized
  19. customthis was collected
  20. customdried in vacuo

Sources & evidence

ORD record
ord-337c9b70c92446b5aa8599ff7e5817dc
Source dataset
uspto-grants-1993_08
Patent number
US05236931

Reaction notes

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