Oxalic Acid → (2R)-N-(piperidin-4-yl)oxolane-2-carboxamide

HRID 2062283Notes

Reaction equation

HRID 2062283 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([C@H:17]2[CH2:21][CH2:20][CH2:19][O:18]2)=[O:16])[CH2:10][CH2:9]1)C1C=CC=CC=1.[H][H].C(O)(=O)C(O)=O>C(O)C.C(O)(=O)C.[Pd].CC(O)C>[NH:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([C@H:17]2[CH2:21][CH2:20][CH2:19][O:18]2)=[O:16])[CH2:10][CH2:9]1

Participants

8

Reactant 3

HCID 971Oxalic AcidHCID 1246648(R)-tetrahydrofuran-2-carboxylic acid (1-benzyl-piperidin-4-yl)-amideHCID 178418361HCID 178418361, compound2×

Product 1

HCID 28810902(2R)-N-(piperidin-4-yl)oxolane-2-carboxamide

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 3776IsopropanolSolvent

Procedure

(R)-Tetrahydro-furan-2-carboxylic acid (1-benzyl-piperidin-4-yl)-amide (128 g, 444 mmol) was dissolved in 300 mL ethanol and 50 mL acetic acid. Palladium on activated carbon (5 g) was added. A hydrogen pressure of 5 bars was applied, and hydrogenation was continued until no more hydrogen was consumed (about 5 days). The suspension was filtered through Celite, and the filtrate was evaporated to dryness under reduced pressure. The residue and oxalic acid (50 g, 555 mmol) were suspended in 500 mL 2-propanol and heated to dissolve the solids. Upon cooling, the oxalate salt of R-tetrahydro-furan-2-carboxylic acid piperidin-4-ylamide crystallized and was collected by filtration to yield (R)-Tetrahydro-furan-2-carboxylic acid piperidin-4-ylamide as an oxalate salt (99.0 g, 77%) as an off-white solid. 1H-NMR (300 MHz, DMSO-d6): δ 7.84 (d, J=7.8 Hz, 1H), 5.90 (bs, 2H), 4.18-4.14 (m, 1H), 3.89-3.67 (m, 3H), 3.25-3.20 (m, 2H), 2.94-2.71 (m, 2H), 2.13-2.00 (m, 1H), 1.56-1.58 (m, 6H) ppm.

Workup

  1. customwas consumed (about 5 days)
  2. filtrationThe suspension was filtered through Celite
  3. customthe filtrate was evaporated to dryness under reduced pressure
  4. temperatureheated
  5. dissolutionto dissolve the solids
  6. temperatureUpon cooling
  7. customthe oxalate salt of R-tetrahydro-furan-2-carboxylic acid piperidin-4-ylamide crystallized
  8. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-ade94e296cd34a3b905ea84b406e1dfa
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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