Triethylamine → (S)-tert-butyl 4-(methylthio)-4-oxo-2-(pent-4-enamido)butanoate

HRID 1482182Notes

Reaction equation

HRID 1482182 reaction equation
CCN(CC)CC.C(Cl)(=O)OCC.[C:14]([O:18][C:19](=[O:32])[C@@H:20]([NH:25][C:26](=[O:31])[CH2:27][CH2:28][CH:29]=[CH2:30])[CH2:21][C:22](O)=[O:23])([CH3:17])([CH3:16])[CH3:15].C(O)(=O)CCC=C.[CH3:40][S-:41].[Na+]>C1COCC1.CN(C=O)C.ClCCl.O>[CH3:40][S:41][C:22](=[O:23])[CH2:21][C@H:20]([NH:25][C:26](=[O:31])[CH2:27][CH2:28][CH:29]=[CH2:30])[C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:32]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 611384-Pentenoic acidHCID 4378561Sodium methanethiolateHCID 89668326(S)-4-(tert-butoxy)-4-oxo-3-(pent-4-enamido)butanoic acid2×

Product 1

HCID 89668258(S)-tert-butyl 4-(methylthio)-4-oxo-2-(pent-4-enamido)butanoateYield 85%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Et3N (1.54 ml, 11.0 mmol) and ethyl carbonochloridate (1.05 ml, 11.0 mmol) were added to a solution of the mixed crude product A (1.96 g, 9.68 mmol) of (S)-4-(tert-butoxy)-4-oxo-3-(pent-4-enamido)butanoic acid (Compound 1b-I) and pent-4-enoic acid (1:0.8) in THF (44 ml), and the mixture was stirred at room temperature for 25 minutes. A solution of sodium methanethiolate (1.06 g, 15.1 mmol) in DMF (18 ml) was then added to the reaction mixture, which was stirred at room temperature for 1 hour. Water was then added to the reaction mixture, followed by dilution with dichloromethane. The organic layer was washed with water, and then dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography (10 mM aqueous ammonium acetate solution/methanol=70/30→40/60) to afford (S)-tert-butyl 4-(methylthio)-4-oxo-2-(pent-4-enamido)butanoate (Compound 1e-IA) (1.38 g, 85%).

Workup

  1. stirringwas stirred at room temperature for 1 hour
  2. washThe organic layer was washed with water
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by reverse-phase silica gel column chromatography (10 mM aqueous ammonium acetate solution/methanol=70/30→40/60)

Sources & evidence

ORD record
ord-4019ee343b7b496c97fea462e6932ad0
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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