Hydrochloric Acid → 1-(8-Fluoroquinolin-7-yl)piperidin-4-one

HRID 2241984Notes

Reaction equation

HRID 2241984 reaction equation
O1[C:5]2([CH2:10][CH2:9][N:8]([C:11]3[C:20]([F:21])=[C:19]4[C:14]([CH:15]=[CH:16][CH:17]=[N:18]4)=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[O:4]CC1.Cl.[OH-].[Na+]>O1CCCC1>[F:21][C:20]1[C:11]([N:8]2[CH2:7][CH2:6][C:5](=[O:4])[CH2:10][CH2:9]2)=[CH:12][CH:13]=[C:14]2[C:19]=1[N:18]=[CH:17][CH:16]=[CH:15]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 592048707-(1.4-Dioxa-8-azaspiro[4.5]dec-8-yl)-8-fluoroquinoline

Product 1

HCID 592048601-(8-Fluoroquinolin-7-yl)piperidin-4-oneYield 80.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-(1.4-dioxa-8-azaspiro[4.5]dec-8-yl)-8-fluoroquinoline (Example J, Step 2; 1.30 g) in tetrahydrofuran (60 mL) was added aq. 2N aqueous HCl (10 mL). The resulting mixture was stirred at room temperature for 18 hours and then heated at 60° C. for 5 hours. The reaction mixture was cooled to room temperature, poured into 1N aqueous NaOH and extracted with ethyl acetate. The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated on a rotary evaporator. The crude product was purified by flash chromatography using hexane/acetone to give 0.89 g of the desired product as a yellow solid; MS (ES) m/z (relative intensity): 245 (M+H)+ (100).

Workup

  1. temperatureheated at 60° C. for 5 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated on a rotary evaporator
  7. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-7480e53ad55441b9859bfbb6fbfbaac9
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Reaction notes

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