1,4-Dioxane → 4-(1-(5-Chloro-2-(3-((3-fluorophenoxy)methyl)pyrrolidin-1-yl)nicotinamido)cyclopropyl)benzoic acid

HRID 72556Notes

Reaction equation

HRID 72556 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:24]2[CH2:28][CH2:27][CH:26]([CH2:29][O:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=3)[CH2:25]2)=[C:6]([CH:23]=1)[C:7]([NH:9][C:10]1([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19]C)=[O:18])=[CH:15][CH:14]=2)[CH2:12][CH2:11]1)=[O:8].O1CCOCC1.O.[OH-].[Li+]>O>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:24]2[CH2:28][CH2:27][CH:26]([CH2:29][O:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=3)[CH2:25]2)=[C:6]([CH:23]=1)[C:7]([NH:9][C:10]1([C:13]2[CH:22]=[CH:21][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=2)[CH2:12][CH2:11]1)=[O:8]

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 168937Lithium hydroxide, monohydrateHCID 67958339Methyl 4-(1-(5-chloro-2-(3-((3-fluorophenoxy)methyl)pyrrolidin-1-yl)nicotinamido)cyclopropyl)benzoate

Product 1

HCID 573773554-(1-(5-Chloro-2-(3-((3-fluorophenoxy)methyl)pyrrolidin-1-yl)nicotinamido)cyclopropyl)benzoic acidYield 51%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of methyl 4-(1-(5-chloro-2-(3-((3-fluorophenoxy)methyl)pyrrolidin-1-yl)nicotinamido)cyclopropyl)benzoate (D200) (37 mg, 0.070 mmol) in a mixture 1,4-dioxane and water (3:1) (2 ml) lithium hydroxide monohydrate (10 mg, 0.238 mmol) was added and the mixture was stirred 20 min (4 cycles of 5 min each) under microwaves irradiation. After solvent evaporation the residue was diluted with water (5 ml) and 1M HCl (5 ml) and extracted with ethylacetate (3×10 ml). Collected organics after solvent evaporation afforded a residue that was purified by ISOLUTE Spe-Si (1 g) eluting with a mixture dichloromethane/methanol 98:2. Collected fractions after solvent evaporation afforded the title compound (E76) (18.2 mg)

Workup

  1. customunder microwaves irradiation
  2. customAfter solvent evaporation the residue
  3. additionwas diluted with water (5 ml) and 1M HCl (5 ml)
  4. extractionextracted with ethylacetate (3×10 ml)
  5. customCollected organics after solvent evaporation
  6. customafforded a residue that
  7. customwas purified by ISOLUTE Spe-Si (1 g)
  8. washeluting with a mixture dichloromethane/methanol 98:2
  9. customCollected fractions after solvent evaporation

Sources & evidence

ORD record
ord-75ba6ba62431407f8959d271c8005641
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Reaction notes

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