Formaldehyde → 4,6,6-Trimethylmorpholine-3-carboxylic acid

HRID 12192Notes

Reaction equation

HRID 12192 reaction equation
[CH3:1][C:2]1([CH3:11])[CH2:7][NH:6][CH:5]([C:8]([OH:10])=[O:9])[CH2:4][O:3]1.[CH2:12]=O>C(O)C.[Pd]>[CH3:12][N:6]1[CH2:7][C:2]([CH3:11])([CH3:1])[O:3][CH2:4][CH:5]1[C:8]([OH:10])=[O:9]

Participants

5

Reactant 2

HCID 712FormaldehydeHCID 457913486,6-Dimethylmorpholine-3-carboxylic acid2×

Product 1

HCID 671654624,6,6-Trimethylmorpholine-3-carboxylic acidYield 97%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a suspension of 6,6-dimethyl-morpholine-3-carboxylic acid (Intermediate 19, 540 mg) in 17 ml of ethanol (under nitrogen) was added 100 mg of 10% Pd on charcoal and 830 ul (˜3 eq.) of 37% aqueous formaldehyde. The mixture was purged with hydrogen (balloon) and stirred at ambient temperature for 5 hrs. To the resulting gray mixture were added 4 ml of water and 4 ml of methanol to help dissolution. The catalyst was removed by filtration and the filtrate was concentrated to dryness. The residue was triturated with EtOAc. The generated white solid was filtered off and dried under high vacuum to give 574 mg of 4,6,6-trimethyl-morpholine-3-carboxylic acid (97% yield).

Workup

  1. customThe mixture was purged with hydrogen (balloon)
  2. additionTo the resulting gray mixture were added 4 ml of water and 4 ml of methanol
  3. dissolutiondissolution
  4. customThe catalyst was removed by filtration
  5. concentrationthe filtrate was concentrated to dryness
  6. customThe residue was triturated with EtOAc
  7. filtrationThe generated white solid was filtered off
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-922f4d1b3fc74bca99bd38351a87de4c
Source dataset
uspto-grants-2010_06
Patent number
US07727985B2

Reaction notes

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