Formaldehyde → (S)-4-Methyl-2-[methyl-(tetrahydro-pyran-4-yl)-amino]-pentanoic acid

HRID 990352Notes

Reaction equation

HRID 990352 reaction equation
[CH3:1][CH:2]([CH3:15])[CH2:3][C@H:4]([NH:8][CH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)[C:5]([OH:7])=[O:6].[CH2:16]=O.[H][H]>C(O)C.[Pd]>[CH3:1][CH:2]([CH3:15])[CH2:3][C@H:4]([N:8]([CH3:16])[CH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)[C:5]([OH:7])=[O:6]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 15458709HCID 15458709, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 15458710(S)-4-Methyl-2-[methyl-(tetrahydro-pyran-4-yl)-amino]-pentanoic acidYield 92.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of (S)-4-methyl-2-(tetrahydro-pyran-4-ylamino)-pentanoic acid (9.09 g, 42.3 mmol, Example 18, Step A) and aqueous HCHO (10 mL of 37.2%, 3.72 g, 124 mmol) was agitated in an atmosphere of hydrogen (pressure, 47-52 psi) at 50° C. in absolute ethanol (250 mL) in the presence of Pd/C (20%, 1 g) until the absorption of hydrogen almost ceased. The catalyst was removed by filtration. The filtrate was concentrated in vacuo to dryness. Fifty milliliter of water was added and concentrated to dryness, and this operation was repeated twice to remove most of HCHO. Absolute ethanol (50 mL) was then added and concentrated to dryness to remove residual water. The white solid collected was triturated with acetone. Filtration and drying under vacuum gave 8.93 g (92%) of the desired product as a white solid; mp 185-190° C. (decomposed). APCI-MS m/z 230.2 (MH+).

Workup

  1. customThe catalyst was removed by filtration
  2. concentrationThe filtrate was concentrated in vacuo to dryness
  3. additionFifty milliliter of water was added
  4. concentrationconcentrated to dryness
  5. customto remove most of HCHO
  6. additionAbsolute ethanol (50 mL) was then added
  7. concentrationconcentrated to dryness
  8. customto remove residual water
  9. customThe white solid collected
  10. customwas triturated with acetone
  11. filtrationFiltration
  12. customdrying under vacuum

Sources & evidence

ORD record
ord-c68ff3794006412a9222fe5d7c900593
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

Loading…