trans-1-Boc-4-aminomethyl-3-hydroxypiperidine → (+/-)-1,1-Dimethylethyl trans-4-[[(4-amino-5-chloro-2,3-dimethoxybenzoyl)amino]methyl]-3-hydroxy-1-piperidinecarboxylate

HRID 1281101Notes

Reaction equation

HRID 1281101 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:30]([Cl:31])=[CH:29][C:21]([C:22](N2C=CN=C2)=[O:23])=[C:20]([O:32][CH3:33])[C:19]=1[O:34][CH3:35]>C(#N)C>[NH2:17][C:18]1[C:30]([Cl:31])=[CH:29][C:21]([C:22]([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:23])=[C:20]([O:32][CH3:33])[C:19]=1[O:34][CH3:35]

Participants

4

Reactant 2

HCID 11075229trans-1-Boc-4-aminomethyl-3-hydroxypiperidineHCID 88040818HCID 88040818, compound

Product 1

HCID 11015727(+/-)-1,1-Dimethylethyl trans-4-[[(4-amino-5-chloro-2,3-dimethoxybenzoyl)amino]methyl]-3-hydroxy-1-piperidinecarboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate (1-e) (0.087 mol) and intermediate (3-a) (0.087 mol) in acetonitrile (600 ml) was stirred and refluxed for 90 min. The reaction mixture was cooled, 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 suspended in DIPE with a drop of ACN, filtered off and dried (vacuum, 40° C.), yielding 30.3 g (80%) of (±)-1,1-dimethylethyl trans-4-[[(4-amino-5-chloro-2,3-dimethoxybenzoyl)amino]methyl]-3-hydroxy-1-piperidinecarboxylate (interm. 4).

Workup

  1. temperaturerefluxed for 90 min
  2. temperatureThe reaction mixture was cooled
  3. customthe solvent was evaporated
  4. customThe residue was partitioned between DCM and water
  5. customThe organic layer was separated
  6. customdried
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. filtrationfiltered off
  10. customdried (vacuum, 40° C.)

Sources & evidence

ORD record
ord-b127e554c2a3451ea46780ddcebabbd4
Source dataset
uspto-grants-2002_09
Patent number
US06452013B1

Reaction notes

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