Sodium Carbonate → methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(pyridin-3-yl)propanoate

HRID 397015Notes

Reaction equation

HRID 397015 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([OH:19])=[O:18])[CH2:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(Cl)(Cl)=O.[C:24](OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(=O)([O-])[O-].[Na+].[Na+]>CO.C(OCC)(=O)C>[CH3:24][O:18][C:17](=[O:19])[C@H:9]([CH2:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 90495Di-tert-butyl dicarbonateHCID 7020919Boc-3-(3-pyridyl)-Ala-OH

Product 1

HCID 15337847methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(pyridin-3-yl)propanoateYield 75.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(t-butoxycarbonyl)-3-(3-pyridyl)alanine (5.0 g, 18.8 mmole) in methanol (100 mL) was added thionyl chloride (2M solution in dichloromethane, 66 mL, 132 mmole). The resulting solution was stirred overnight at ambient temperature. The methanol was removed under reduced pressure to a minimum volume and ethyl acetate (100 mL) was added. The resulting white precipitate was collected in a fritted funnel. To a solution of the collected precipitate in a mixture of tetrahydrofuran/water (40 mL each) was added di-tert-butyl dicarbonate (4.8 g, 21.99 mmole) and sodium carbonate (1.95 g, 18.4 mmole). After stirring for 12 hours at ambient temperature, the reaction mixture was diluted with ethyl acetate (40 mL) and washed with a solution of saturated sodium bicarbonate (25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to give crude product. This product was subjected to flash column chromatography on silica gel (230-400 mesh) using a 8×52 cm column and eluting with a 10:90 mixture of ethyl acetate/hexane followed by a 60:40 mixture of ethyl acetate/hexane. 4 g (74%) of the title compound was obtained as an oil. Thin-layer chromatography gave a Rf=0.68 (silica gel; ethyl acetate).

Workup

  1. customThe methanol was removed under reduced pressure to a minimum volume and ethyl acetate (100 mL)
  2. additionwas added
  3. customThe resulting white precipitate was collected in a fritted funnel
  4. additionTo a solution of the collected precipitate in a mixture of tetrahydrofuran/water (40 mL each)
  5. stirringAfter stirring for 12 hours at ambient temperature
  6. washwashed with a solution of saturated sodium bicarbonate (25 mL)
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customto give crude product
  10. washeluting with a 10:90 mixture of ethyl acetate/hexane
  11. additionfollowed by a 60:40 mixture of ethyl acetate/hexane

Sources & evidence

ORD record
ord-e69f2c579fbf492889d3d41531536a23
Source dataset
uspto-grants-2003_08
Patent number
US06608204B1

Reaction notes

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