Hydrochloric Acid → 2-Nitro-4-piperidin-1-ylmethyl-benzoic acid hydrochloride

HRID 512965Notes

Reaction equation

HRID 512965 reaction equation
C([O:5][C:6](=[O:24])[C:7]1[CH:12]=[CH:11][C:10]([C:13]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=O)=[CH:9][C:8]=1[N+:21]([O-:23])=[O:22])(C)(C)C.[ClH:25].C([O-])([O-])=O.[K+].[K+]>C1COCC1.C(Cl)Cl.O1CCOCC1>[ClH:25].[N+:21]([C:8]1[CH:9]=[C:10]([CH2:13][N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:11]=[CH:12][C:7]=1[C:6]([OH:24])=[O:5])([O-:23])=[O:22]

Participants

7

Reactant 3

HCID 313Hydrochloric Acid2×HCID 11430Potassium CarbonateHCID 686720862-Nitro-4-(piperidine-1-carbonyl)-benzoic acid tert-butyl ester

Product 1

HCID 686710012-Nitro-4-piperidin-1-ylmethyl-benzoic acid hydrochloride

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

2-Nitro-4-(piperidine-1-carbonyl)-benzoic acid tert-butyl ester (1.87 mmol) was dissolved in dry THF and added drop-wise to 3.7 mL of borane tetrahydrofuran complex 1.0 M solution, at room temperature, under nitrogen, with stirring. The reaction was then refluxed for six hours, cooled to room temperature and treated carefully with 2N HCl (10 mL) After stirring for 15 minutes, solid K2CO3 was added in portions (1.75 g). The mixture was extracted with EtOAc (3×25 mL). The combined organic layers were dried over sodium sulphate and evaporated leaving an oil that by HPLC-MS analysis resulted a 4:6 mixture of the tertiary amine and the corresponding borane complex. The mixture was dissolved in DCM (1 mL) and treated with 4N HCl in dioxane (7 mL). After 4 days at room temperature, an off white was formed which was filtered, washed with dioxane (5 mL) and dried at 50° C. under vacuum. 0.40 g of title compound were obtained in 70% overall yield.

Workup

  1. additionadded drop-wise to 3.7 mL of borane tetrahydrofuran complex 1.0 M solution
  2. temperatureThe reaction was then refluxed for six hours
  3. temperaturecooled to room temperature
  4. stirringAfter stirring for 15 minutes
  5. extractionThe mixture was extracted with EtOAc (3×25 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulphate
  7. customevaporated
  8. customleaving an oil that by HPLC-MS analysis
  9. customresulted
  10. customan off white was formed which
  11. filtrationwas filtered
  12. washwashed with dioxane (5 mL)
  13. customdried at 50° C. under vacuum

Sources & evidence

ORD record
ord-21c16b555e4a4239ac2d21ed2beb42d9
Source dataset
uspto-grants-2015_08
Patent number
US09102662B2

Reaction notes

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