(4-Amino-5-chloro-2,3-dihydrobenzofuran-7-yl)(1H-imidazol-1-yl)methanone → (+/-)-1,1-Dimethylethyl cis-4-[[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate

HRID 988122Notes

Reaction equation

HRID 988122 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][C@H:4]1[OH:16].[NH2:17][C:18]1[C:23]2[CH2:24][CH2:25][O:26][C:22]=2[C:21]([C:27](N2C=CN=C2)=[O:28])=[CH:20][C:19]=1[Cl:34]>C(#N)C>[NH2:17][C:18]1[C:23]2[CH2:24][CH2:25][O:26][C:22]=2[C:21]([C:27]([NH:1][CH2:2][C@H:3]2[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:10])[CH2:5][C@H:4]2[OH:16])=[O:28])=[CH:20][C:19]=1[Cl:34]

Participants

4

Reactant 2

HCID 22662740(4-Amino-5-chloro-2,3-dihydrobenzofuran-7-yl)(1H-imidazol-1-yl)methanoneHCID 57983247Tert-butyl (3s,4r)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate

Product 1

HCID 131724101(+/-)-1,1-Dimethylethyl cis-4-[[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of intermediate (1-f) (0.09 mol) and intermediate (3-c) (0.087 mol) in ACN (600 ml) was stirred and refluxed for 1 hour. The reaction mixture was cooled to 0° C., and the solvent was evaporated. The residue was partitioned between DCM and water. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 97/3). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from ACN. The precipitate was filtered off and dried), yielding 28.7 g (78%) of (±)-1,1-dimethylethyl cis-4-[[[(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate (interm. 4. mp. 218° C.).

Workup

  1. temperaturerefluxed for 1 hour
  2. customthe solvent was evaporated
  3. customThe residue was partitioned between DCM and water
  4. customThe organic layer was separated
  5. customdried
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 97/3)
  9. customThe pure fractions were collected
  10. customthe solvent was evaporated
  11. customThe residue was crystallized from ACN
  12. filtrationThe precipitate was filtered off
  13. customdried),

Sources & evidence

ORD record
ord-4d6e5ddb45fd4cde94ff6b00b3ec3b93
Source dataset
uspto-grants-2003_10
Patent number
US06635643B2

Reaction notes

Loading…