Oxalic acid dihydrate → Benzyl (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate oxalate

HRID 925521Notes

Reaction equation

HRID 925521 reaction equation
[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[CH2:7]([O:14][NH:15][CH:16]1[CH2:21][NH:20][CH:19]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:18][CH2:17]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(=O)(O)[O-].[K+].O.O.C(O)(=O)C(O)=O>C(OCC)(=O)C.O.CO>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[CH2:7]([O:14][NH:15][C@H:16]1[CH2:21][NH:20][C@H:19]([C:22]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[CH2:18][CH2:17]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 3

HCID 61373Oxalic acid dihydrateHCID 516893Potassium BicarbonateHCID 77895673Benzyl 5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate

Product 1

HCID 70673933Benzyl (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate oxalate

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a slurry of benzyl 5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate (1:1) (10 g, 23.3 mmol, 3:1, SR:SS) in ethyl acetate (70 ml) was added a solution of potassium bicarbonate (9.3 g, 93 mmol, 4 eq) in water (90 ml). The mixture was stirred until all the solids had dissolved. The layers were separated and the aqueous layer was extracted with ethyl acetate (30 ml). The combined organic layers were washed with water (50 ml) and concentrated under vacuum below 40° C. to a final volume of 40 ml. The solution was passed through a filter and warmed to 45° C. Methanol (20 ml) at 40° C. was added, followed by a freshly prepared solution of oxalic acid dihydrate (3.67 g, 29.1 mmol) in methanol (10 ml). The mixture was cooled and the product was isolated by filtration. The solid was washed with an ethyl acetate/methanol mixture, then with ethyl acetate. The solid was dried to give benzyl (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate (1:1) as a single isomer (7.0 g, 16.3 mmol, 70%).

Workup

  1. dissolutionhad dissolved
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (30 ml)
  4. washThe combined organic layers were washed with water (50 ml)
  5. concentrationconcentrated under vacuum below 40° C. to a final volume of 40 ml
  6. filtrationa filter
  7. additionMethanol (20 ml) at 40° C. was added
  8. temperatureThe mixture was cooled
  9. customthe product was isolated by filtration
  10. washThe solid was washed with an ethyl acetate/methanol mixture
  11. customThe solid was dried

Sources & evidence

ORD record
ord-37da2ba13b0d4f31a491d00a0adfb8bc
Source dataset
uspto-grants-2016_03
Patent number
US09284314B2

Reaction notes

Loading…