1,1'-Carbonyldiimidazole → 4-Amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-2-hydroxybenzamide

HRID 1091045Notes

Reaction equation

HRID 1091045 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([OH:12])[CH:3]=1.[C:13]([N:20]1[CH:24]=[CH:23][N:22]=[CH:21]1)(N1C=CN=C1)=O.[C:25]1(N)[C:30](F)=C(F)C(F)=C(N)[C:26]=1F.Cl.Cl>O1CCCC1.CCOCC>[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([NH:22][CH:23]2[CH:25]3[CH2:30][CH2:13][N:20]([CH2:21][CH2:26]3)[CH2:24]2)=[O:8])=[C:4]([OH:12])[CH:3]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 148832224-Amino-5-chloro-2-hydroxybenzoic acid

Product 1

HCID 156708204-Amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-2-hydroxybenzamideYield 90%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-amino-5-chloro-2-hydroxybenzoic acid (5.63 g, 30 mmole) in anhydrous tetrahydrofuran (30 ml) under nitrogen is treated with 1,1'-carbonyldiimidazole (5.03 g, 31 mmole), stirred at room temperature for one hour, and degassed by bubbling nitrogen over 20 minutes. A solution of 3-aminoquinuclidine(1) (from 36 mmole of the dihydrochloride) in anhydrous tetrahydrofuran (20 ml) is added, and the mixture is stirred at room temperature for 18 hours and at 50° C. for one hour. The resultant suspension is diluted with ether (50 ml) and filtered, and the solid is washed with ether. Successive trituration from acetonitrile and warm methanol provides 7.95 g (90%) of product as a pale tan solid, mp 300°-302° C. (dec.).

Workup

  1. customdegassed
  2. customby bubbling nitrogen over 20 minutes
  3. stirringthe mixture is stirred at room temperature for 18 hours and at 50° C. for one hour
  4. filtrationfiltered
  5. washthe solid is washed with ether
  6. temperatureSuccessive trituration from acetonitrile and warm methanol

Sources & evidence

ORD record
ord-74e3519e5a994ba394564226f9a25301
Source dataset
uspto-grants-1992_01
Patent number
US05084460

Reaction notes

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