1-Naphthaleneacetic Acid → HCID 22261436, compound

HRID 1610227Notes

Reaction equation

HRID 1610227 reaction equation
[C:1]1([CH2:11][C:12]([OH:14])=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.Cl.[F:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]([OH:43])[CH:30]([NH2:42])[CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=2)=[CH:25][CH:24]=1.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[F:22][C:23]1[CH:24]=[CH:25][C:26]([CH:29]([OH:43])[CH:30]([NH:42][C:12](=[O:14])[CH2:11][C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)[CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=2)=[CH:27][CH:28]=1

Participants

9

Reactant 4

HCID 68621-Naphthaleneacetic AcidHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 22261728(1RS,2RS)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride

Product 1

HCID 22261436HCID 22261436, compoundYield 64%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-naphthaleneacetic acid (160 mg, 0.86 mmol) in tetrahydrofuran (5 ml) were added oxalyl chloride (0.15 ml, 1.72 mmol) and N,N-dimethylformamide (0.01 ml), and the mixture was stirred at room temperature for 30 min. The reaction solution was evaporated under reduced pressure. To a solution of the residue in ethyl acetate (5 ml) were added (1RS,2SR)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride (200 mg, 0.57 mmol) and saturated aqueous sodium hydrogen carbonate (5 ml) and the mixture was stirred at room temperature for 2 hrs. The reaction solution was diluted with water (50 ml), and extracted with ethyl acetate (50 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:1). Recrystallization from ethyl acetate-hexane gave the title compound (175 mg, 64%).

Workup

  1. customThe reaction solution was evaporated under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 2 hrs
  3. extractionextracted with ethyl acetate (50 ml×2)
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:1)
  8. customRecrystallization from ethyl acetate-hexane

Sources & evidence

ORD record
ord-3fc3e5fbbc1d4a38995aa197ad286795
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

Loading…