Hydrochloric Acid → benzyl (2S,4R)-2-{[methoxy(methyl)amino]carbonyl}-4-(tetrahydro-2H-pyran-2-yloxy)-1-pyrrolidine-carboxylate

HRID 2249674Notes

Reaction equation

HRID 2249674 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C@H:8]1[CH2:12][N:11]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[C@H:10]([C:23]([O:25]CC)=O)[CH2:9]1.[OH-].[Na+].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.Cl.[CH3:48][NH:49][O:50][CH3:51].Cl>C(O)C.CN(C)C=O.O.C(OCC)(=O)C.C(N(CC)CC)C>[CH3:51][O:50][N:49]([CH3:48])[C:23]([C@@H:10]1[CH2:9][C@@H:8]([O:7][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[CH2:12][N:11]1[C:13]([O:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:14])=[O:25]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 199401P,P-Diphenylphosphinic azideHCID 866300501-benzyl 2-ethyl (2S,4R)-4-(tetrahydro-2H-pyran-2-yloxy)-1,2-pyrrolidinedicarboxylate

Product 1

HCID 86630051benzyl (2S,4R)-2-{[methoxy(methyl)amino]carbonyl}-4-(tetrahydro-2H-pyran-2-yloxy)-1-pyrrolidine-carboxylateYield 28.4%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 127 ml of ethanol is dissolved 12.7 g of 1-benzyl 2-ethyl (2S,4R)-4-(tetrahydro-2H-pyran-2-yloxy)-1,2-pyrrolidinedicarboxylate. After adding 37.0 ml of 1 mol/L sodium hydroxide solution at 5-10° C., the mixture thus obtained is stirred at ambient temperature for 1.5 hours. The solvent is distilled off from the reaction mixture under reduce pressure, the residue thus obtained is dissolved in 90 ml of N,N-dimethylformamide, 10.9 ml of diphenylphosphoryl azide, 14.1 ml of triethylamine and 3.94 g of N,O-dimethylhydroxylamine hydrochloride are successively added at 5-10° C., and the mixture thus obtained is stirred at ambient temperature for one hour. Ethyl acetate and water are added to the reaction mixture, pH is adjusted to 6.5 with 6 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with water and saturated aqueous solution of sodium chloride successively and dried over anhydrous sodium sulfate, and then the solvent is distilled off under reduced pressure. The residue thus obtained is purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=4:1) to obtain 3.75 g of benzyl (2S,4R)-2-{[methoxy(methyl)amino]carbonyl}-4-(tetrahydro-2H-pyran-2-yloxy)-1-pyrrolidinecarboxylate as a light yellow oily product.

Workup

  1. customthe mixture thus obtained
  2. distillationThe solvent is distilled off from the reaction mixture
  3. customthe residue thus obtained
  4. customthe mixture thus obtained
  5. stirringis stirred at ambient temperature for one hour
  6. customthe organic layer is separated
  7. washThe organic layer is washed with water and saturated aqueous solution of sodium chloride successively
  8. dry with materialdried over anhydrous sodium sulfate
  9. distillationthe solvent is distilled off under reduced pressure
  10. customThe residue thus obtained
  11. customis purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-f1807a67e8c14361a46a97e165da61fd
Source dataset
uspto-grants-2008_01
Patent number
US07314888B1

Reaction notes

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