Pyridine → tert-Butyl N-allyl-N-[2-hydroxyimino-2-isothiazol-5-yl-ethyl]carbamate

HRID 470219Notes

Reaction equation

HRID 470219 reaction equation
[CH2:1]([N:4]([CH2:12][C:13]([C:15]1[S:19][N:18]=[CH:17][CH:16]=1)=O)[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[CH:2]=[CH2:3].N1C=CC=CC=1.Cl.[NH2:27][OH:28]>C(O)C>[CH2:1]([N:4]([CH2:12][C:13](=[N:27][OH:28])[C:15]1[S:19][N:18]=[CH:17][CH:16]=1)[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 1049PyridineHCID 443297Hydroxyamine hydrochlorideHCID 86697894tert-Butyl N-allyl-N-(2-isothiazol-5-yl-2-oxo-ethyl)carbamate

Product 1

HCID 136378630tert-Butyl N-allyl-N-[2-hydroxyimino-2-isothiazol-5-yl-ethyl]carbamate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a room temperature solution of tert-butyl N-allyl-N-(2-isothiazol-5-yl-2-oxo-ethyl)carbamate (5.93 g, 21.00 mmol) in ethanol (70 mL) is added pyridine (5.94 mL, 73.50 mmol) and hydroxylamine hydrochloride (3.65 g, 52.50 mmol). The mixture is heated to reflux for 4 hours. The mixture is allowed to cool to room temperature and is then concentrated under reduced pressure. The resulting crude product is diluted with ethyl acetate (200 mL) and washed with saturated sodium bicarbonate (150 mL). The aqueous layer is re-extracted with ethyl acetate (2×100 mL). The combined organic layers are dried over sodium sulfate, filtered, and the solvent is removed under vacuum. The crude product is purified by silica gel column chromatography using a 15 minute, 0% to 20% ethyl acetate in dichloromethane gradient, to give the title compound as a mixture of E and Z isomers (5.62 g, 18.90 mmol, 90%). ES/MS (m/e): 298 (M+H).

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 4 hours
  3. concentrationis then concentrated under reduced pressure
  4. additionThe resulting crude product is diluted with ethyl acetate (200 mL)
  5. washwashed with saturated sodium bicarbonate (150 mL)
  6. extractionThe aqueous layer is re-extracted with ethyl acetate (2×100 mL)
  7. dry with materialThe combined organic layers are dried over sodium sulfate
  8. filtrationfiltered
  9. customthe solvent is removed under vacuum
  10. customThe crude product is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-81dabb5f0233433cac83ac842496e118
Source dataset
uspto-grants-2014_01
Patent number
US08629270B2

Reaction notes

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