Propionic Acid → Ethyl (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate oxalate

HRID 925523Notes

Reaction equation

HRID 925523 reaction equation
C(O)(=O)CC.[BH4-].[Na+].[CH2:8]([O:10][C:11]([C@@H:13]1[CH2:18][CH2:17][C:16](=[N:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:15][NH:14]1)=[O:12])[CH3:9].S(=O)(=O)(O)O.O.O.[C:35]([OH:40])(=[O:39])[C:36]([OH:38])=[O:37]>C(OCC)(=O)C.C(O)C>[C:35]([OH:40])(=[O:39])[C:36]([OH:38])=[O:37].[CH2:21]([O:20][NH:19][C@H:16]1[CH2:15][NH:14][C@H:13]([C:11]([O:10][CH2:8][CH3:9])=[O:12])[CH2:18][CH2:17]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

8

Reactant 5

HCID 1032Propionic AcidHCID 1118Sulfuric AcidHCID 61373Oxalic acid dihydrateHCID 4311764Sodium borohydrideHCID 86675006HCID 86675006, compound

Product 1

HCID 86675004Ethyl (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate oxalate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
45 °C

Procedure

Propanoic acid (34.9 ml, 466.2 mmol, 6 eq) was added to a suspension of sodium borohydride (5.75 g, 155.4 mmol, 2 eq) in ethyl acetate (160 ml) and held until the reaction was deemed to be complete. The resulting solution was added to a solution of (S)-5-Benzyloxyimino-piperidine-2-carboxylic acid ethyl ester in ethyl acetate (120 ml total volume) and sulfuric acid (20.7 ml, 388.5 mmol, 5 eq) at −20° C. and held until reaction was deemed to be complete. The reaction was quenched by the addition of water (240 ml), then neutralized with aqueous ammonia solution. The organic layer was washed with water and concentrated in vacuo to 80 ml. The solution was warmed to 45° C. and held at this temperature. Ethanol (80 ml, 95%) at 40° C. was added, followed by a freshly prepared solution of oxalic acid dihydrate (9.8 g, 77.7 mmol) in ethanol (40 ml). The mixture was cooled and the product was isolated by filtration. The solid was washed with an ethyl acetate/ethanol mixture, then with ethyl acetate. The solid was dried to give ethyl (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate (1:1) as a single isomer (16.4 g, 44.5 mmol, 57.3%).

Workup

  1. customheld until reaction
  2. customThe reaction was quenched by the addition of water (240 ml)
  3. washThe organic layer was washed with water
  4. concentrationconcentrated in vacuo to 80 ml
  5. additionEthanol (80 ml, 95%) at 40° C. was added
  6. temperatureThe mixture was cooled
  7. customthe product was isolated by filtration
  8. washThe solid was washed with an ethyl acetate/ethanol mixture
  9. customThe solid was dried

Sources & evidence

ORD record
ord-b0dd0b1350bb4bcf9913ccbdd45eed0d
Source dataset
uspto-grants-2016_03
Patent number
US09284314B2

Reaction notes

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