Formaldehyde → HCID 54444274, compound

HRID 963688Notes

Reaction equation

HRID 963688 reaction equation
C([O:8][C:9](=[O:40])[CH:10]([CH:21]([C:26](=[O:39])[NH:27][CH:28]([C:33](=[O:38])[NH:34][CH:35]1[CH2:37][CH2:36]1)[C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22][CH:23]([CH3:25])[CH3:24])[C:11](OCC1C=CC=CC=1)=O)C1C=CC=CC=1.[H][H].N1CCCCC1.C=O>C(O)C.[Pd]>[CH:35]1([NH:34][C:33]([CH:28]([NH:27][C:26]([CH:21]([C:10](=[CH2:11])[C:9]([OH:40])=[O:8])[CH2:22][CH:23]([CH3:25])[CH3:24])=[O:39])[C:29]([CH3:30])([CH3:32])[CH3:31])=[O:38])[CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8082PiperidineHCID 53820942HCID 53820942, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 54444274HCID 54444274, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

2-[1-(1-Cyclopropylcarbamoyl-2,2-dimethyl-propylcarbamoyl)-3-methyl-butyl]-malonic acid dibenzyl ester (14.53 g, 25.7 mmol) was dissolved in ethanol (200 ml) and the solution was placed under a blanket of argon. 10% Palladium on charcoal (3.2 g) was added and a fine stream of hydrogen gas was passed through the suspension for 3h with stirring. TLC showed that all the starting material had been consumed. The system was purged with argon and the catalyst was removed by filtration. The filtrate was cooled and stirred in an ice bath and treated with piperidine (2.39 g, 28.1 mmol) which was added dropwise, followed by 37% formaldehyde solution (22.6 ml, ca. 257 mmol). The reaction mixture was allowed to warm slowly to room temperature, then stirred overnight. The solvents were removed under reduced pressure and the residual oil was partitioned between ethyl acetate (300 ml) and 1 M hydrochloric acid (300 ml). The organic layer was separated, washed with 1M HCl and brine, dried over MgSO4, filtered and evaporated to dryness. The remaining pale brown foam (4.40 g, crude) contained a number of minor impurities but was used in Step C without purification. 1H-NMR; δ (CDCl3), 8.34 (1H, d, J=10.0 Hz), 7.37 (1H, m), 6.47 (1H, s), 5.99 (1H, s), 4.50 (1H, d, J=9.9 Hz), 4.07 (1H, m), 2.73 (1H, m), 1.79 (1H, m), 1.52 (2H, m), 1.00-0.82 (1 5H, br m), 0.78 (2H, m) and 0.55 (2H, m).

Workup

  1. customhad been consumed
  2. customThe system was purged with argon
  3. customthe catalyst was removed by filtration
  4. temperatureThe filtrate was cooled
  5. stirringstirred in an ice bath
  6. additionwas added dropwise
  7. stirringstirred overnight
  8. customThe solvents were removed under reduced pressure
  9. customthe residual oil was partitioned between ethyl acetate (300 ml) and 1 M hydrochloric acid (300 ml)
  10. customThe organic layer was separated
  11. washwashed with 1M HCl and brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. customevaporated to dryness
  15. customwas used in Step C without purification

Sources & evidence

ORD record
ord-f41d6c0677ff432c8c8d0422f7dafa14
Source dataset
uspto-grants-1998_06
Patent number
US05763621

Reaction notes

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