Dimethylformamide → HCID 19883413, compound

HRID 846607Notes

Reaction equation

HRID 846607 reaction equation
[Cl:1][C:2]1[C:3]([NH:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:27][CH2:28][C:29]1([OH:37])[CH:34]2[CH2:35][CH2:36][N:31]([CH2:32][CH2:33]2)[CH2:30]1.CN(C)C=O>O1CCCC1>[Cl:1][C:2]1[C:3]([NH:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([NH:27][CH2:28][C:29]1([OH:37])[CH:34]2[CH2:33][CH2:32][N:31]([CH2:36][CH2:35]2)[CH2:30]1)=[O:9]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 682631,1'-CarbonyldiimidazoleHCID 116942165-Chloro-2-methoxy-4-(methylamino)benzoic acidHCID 147899783-(Aminomethyl)quinuclidin-3-ol

Product 1

HCID 19883413HCID 19883413, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (3.02 g, 0.014 mole) in anhydrous tetrahydrofuran (15 ml) under nitrogen was treated with 1,1'-carbonyldiimidazole (2.35 g, 0.0145 mole) and stirred for one hour. A solution/suspension of 3-aminomethyl-1-azabicyclo[2.2.2]octan-3-ol (2.34 g, 15 mole) in tetrahydrofuran (15 ml) containing a little N,N-dimethylformamide for solubility was added slowly over a few minutes, and the mixture was stirred overnight (18 hours) at room temperature and for one hour at 60° C., then concentrated in vacuo. The white solid was partitioned between 1.0N sodium carbonate (100 ml) and methylene chloride (200 ml) containing a little methanol, and the organic layer was separated. The aqueous solution was extracted with methylene chloride (2×50 ml) containing a little methanol, and the combined organic solution was dried (sodium sulfate) and passed through a short column of alumina (eluted with 10% methanol/methylene chloride). The filtrate was concentrated in vacuo, triturated from ether, and triturated from acetonitrile to afford 2.67 g (54%) of the title compound as a colorless solid; mp 236°-237° C. (dec).

Workup

  1. additionwas added slowly over a few minutes
  2. stirringthe mixture was stirred overnight (18 hours) at room temperature
  3. waitfor one hour at 60° C.
  4. concentrationconcentrated in vacuo
  5. customThe white solid was partitioned between 1.0N sodium carbonate (100 ml) and methylene chloride (200 ml)
  6. additioncontaining a little methanol
  7. customthe organic layer was separated
  8. extractionThe aqueous solution was extracted with methylene chloride (2×50 ml)
  9. additioncontaining a little methanol
  10. dry with materialthe combined organic solution was dried (sodium sulfate)
  11. concentrationThe filtrate was concentrated in vacuo
  12. customtriturated from ether
  13. customtriturated from acetonitrile

Sources & evidence

ORD record
ord-18b823a95c1743ca9320a248a3b41d1c
Source dataset
uspto-grants-1992_08
Patent number
US05137895

Reaction notes

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