Ammonia → 4-Piperidinylmethyl 4-amino-5-chloro-2-methoxybenzoate

HRID 392065Notes

Reaction equation

HRID 392065 reaction equation
[NH2:1][C:2]1[C:24]([Cl:25])=[CH:23][C:5]([C:6]([O:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)=[O:7])=[C:4]([O:26][CH3:27])[CH:3]=1.N>Cl.C1COCC1>[NH2:1][C:2]1[C:24]([Cl:25])=[CH:23][C:5]([C:6]([O:8][CH2:9][CH:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]2)=[O:7])=[C:4]([O:26][CH3:27])[CH:3]=1

Participants

5

Reactant 2

HCID 222AmmoniaHCID 226627611,1-Dimethylethyl 4-[[(4-amino-5-chloro-2-methoxy-benzoyl)oxy]methyl]-1-piperidine-carboxylate

Product 1

HCID 226627574-Piperidinylmethyl 4-amino-5-chloro-2-methoxybenzoateYield 65%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of intermediate 10 (18 g) in HCl (25 ml) and THF (250 ml) was stirred for 30 minutes at 70° C. The reaction mixture was cooled, alkalized with aqueous ammonia and the layers were separated. The aqueous layer was extracted twice with THF. The combined organic layers were dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (cluent: CH2Cl2/(CH3OH/NH3) 90/10). The pure fractions were collected and the solvent was evaporated. The residue (10 g) was dissolved in CHCl3, washed with aqueous ammonia, dried, filtered and the solvent was evaporated. The residue was suspended in DIPE, filtered off and dried, yielding 8.5 g (65%) 4-piperidinylmethyl 4-amino-5-chloro-2-methoxybenzoate (intermediate 11).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted twice with THF
  4. customThe combined organic layers were dried
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was purified by column chromatography over silica gel (cluent: CH2Cl2/(CH3OH/NH3) 90/10)
  8. customThe pure fractions were collected
  9. customthe solvent was evaporated
  10. dissolutionThe residue (10 g) was dissolved in CHCl3
  11. washwashed with aqueous ammonia
  12. customdried
  13. filtrationfiltered
  14. customthe solvent was evaporated
  15. filtrationfiltered off
  16. customdried

Sources & evidence

ORD record
ord-70855a557e8f4096b3272a87fa6e85e5
Source dataset
uspto-grants-2004_10
Patent number
US06800628B2

Reaction notes

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