Benzaldehyde → HCID 57983094, compound

HRID 1868363Notes

Reaction equation

HRID 1868363 reaction equation
[OH:1][C@H:2]1[C@H:7]([CH2:8][NH:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:6][CH2:5][N:4]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:3]1.[CH:24](=O)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.S1C=CC=C1>[Pd].CO>[C:11]1([CH2:10][N:9]([CH2:8][C@@H:7]2[CH2:6][CH2:5][N:4]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:3][C@H:2]2[OH:1])[CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 240BenzaldehydeHCID 8030ThiopheneHCID 117387271,1-Dimethylethyl (trans)-3-hydroxy4-[[(phenylmethyl)amino]methyl]-1-piperidinecarboxylate

Product 1

HCID 57983094HCID 57983094, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 1,1-dimethylethyl (trans)-3-hydroxy-4-[[(phenylmethyl)amino]methyl]-1-piperidinecarboxylate (intermediate (1-d) in WO-99/02156) (0.426 mol), benzaldehyde (0.5 mol) and palladium-on-carbon (10%) (5 g) in a thiophene solution (5 ml) and methanol (1000 ml) was stirred at 70-80° C. overnight. The solvent was evaporated. The residue was partitioned between DCM (150 ml) and 5% aqueous NaOH (150 ml). The mixture was separated into its layers. The aqueous layer was extracted with DCM. The combined organic layer was dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 90/10). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from DIPE and a drop of ACN. The precipitate was filtered off and dried, yielding 2.35 g 1,1-dimethylethyl (trans)-4-[[bis(phenylmethyl)amino]methyl]-3-hydroxy-1-piperidinecarboxylate (intermediate 27), mp. 133° C.).

Workup

  1. customThe solvent was evaporated
  2. customThe residue was partitioned between DCM (150 ml) and 5% aqueous NaOH (150 ml)
  3. customThe mixture was separated into its layers
  4. extractionThe aqueous layer was extracted with DCM
  5. customThe combined organic layer was dried
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 90/10)
  9. customThe pure fractions were collected
  10. customthe solvent was evaporated
  11. customThe residue was crystallized from DIPE
  12. filtrationThe precipitate was filtered off
  13. customdried

Sources & evidence

ORD record
ord-34c93e5323cd46dba6d4888767574797
Source dataset
uspto-grants-2009_12
Patent number
US07635706B2

Reaction notes

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