Ammonium Hydroxide → 4-Piperidinyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate

HRID 362786Notes

Reaction equation

HRID 362786 reaction equation
[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([O:13][CH:14]2[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]2)=[O:12])=[CH:4][C:3]=1[Cl:27].[NH4+].[OH-]>O1CCCC1.Cl>[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([O:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[O:12])=[CH:4][C:3]=1[Cl:27]

Participants

5

Reactant 2

HCID 14923Ammonium HydroxideHCID 543178411,1-Dimethylethyl 4-[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]oxy]-1-piperidinecarboxylate

Product 1

HCID 545352994-Piperidinyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylateYield 54%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of intermediate (8) (7 g) in tetrahydrofuran (20 ml) and hydrochloric acid (20 ml) was stirred and refluxed for 2 hours. The reaction mixture was cooled and alkalized with NH4OH. The organic layer was removed by decantation and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 92/8). The pure fractions were collected and the solvent was evaporated. The residue (5.5 g) was repurified by high-performance liquid chromatography (column: 200 g Kromasil; 10 μm; 100 Å; eluent: (0.5% NH4OAc in water)/methanol 70/30). The pure fractions were collected and extracted with NH3 /CH2Cl2. The extract was evaporated. The residue was crystallized from acetonitrile. The precipitate was filtered off and dried (vacuum; 70° C.), yielding 2.60 g of 4-piperidinyl 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylate (54%) (intermediate 9).

Workup

  1. temperaturerefluxed for 2 hours
  2. temperatureThe reaction mixture was cooled
  3. customThe organic layer was removed by decantation
  4. customthe solvent was evaporated
  5. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 92/8)
  6. customThe pure fractions were collected
  7. customthe solvent was evaporated
  8. customThe residue (5.5 g) was repurified by high-performance liquid chromatography (column: 200 g Kromasil; 10 μm; 100 Å; eluent: (0.5% NH4OAc in water)/methanol 70/30)
  9. customThe pure fractions were collected
  10. extractionextracted with NH3 /CH2Cl2
  11. customThe extract was evaporated
  12. customThe residue was crystallized from acetonitrile
  13. filtrationThe precipitate was filtered off
  14. customdried (vacuum; 70° C.)

Sources & evidence

ORD record
ord-4bd92c7b7cb846f4b5be1203e78dbd0f
Source dataset
uspto-grants-1999_02
Patent number
US05872131

Reaction notes

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