tert-Butyl Dimethylphosphonoacetate → 6-tert-Butoxycarbonylamino-3-(6-methoxy-pyridin-3-yl)-hex-2-enoic Acid tert-Butyl Ester

HRID 2227260Notes

Reaction equation

HRID 2227260 reaction equation
COP([CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])(OC)=O.C[Si]([NH-])(C)C.C[Si]([NH-])(C)C.[Na+].[Na+].[C:27]([O:31][C:32](=[O:47])[NH:33][CH2:34][CH2:35][CH2:36][C:37]([C:39]1[CH:40]=[N:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=1)=O)([CH3:30])([CH3:29])[CH3:28]>O1CCCC1.C(OCC)(=O)C>[C:11]([O:10][C:8](=[O:9])[CH:7]=[C:37]([C:39]1[CH:40]=[N:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=1)[CH2:36][CH2:35][CH2:34][NH:33][C:32]([O:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:47])([CH3:12])([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 4564495tert-Butyl DimethylphosphonoacetateHCID 22086439[4-(6-Methoxy-pyridin-3-yl)-4-oxo-butyl]-carbamic Acid tert-Butyl EsterHCID 86599718Sodiumbis(trimethylsilylamide)

Product 1

HCID 699879066-tert-Butoxycarbonylamino-3-(6-methoxy-pyridin-3-yl)-hex-2-enoic Acid tert-Butyl Ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of t-butyl dimethylphosphonoacetate (6.86 g, 30.6 mmol) in tetrahydrofuran (150 mL) at −78° C. under argon was added a solution of sodium bis(trimethylsilylamide) (30.6 mL of a 1.0 M solution). After 15 min., a solution of 1-3 (3.0 g, 10.2 mmol) in tetrahydrofuran (30 mL) was added, and the reaction was warmed to ambient temperature, then heated to 40° C. for 1 h. The reaction mixture was then cooled to ambient temperature, diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate, then saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. The reaction mixture was filtered and concentrated at reduced pressure to give an oil that was purified by flash column chromatography (silica gel, 15 to 25% ethyl acetate/hexanes) to give 1-4 and its 2 isomer.

Workup

  1. temperatureheated to 40° C. for 1 h
  2. temperatureThe reaction mixture was then cooled to ambient temperature
  3. washwashed with saturated aqueous sodium hydrogen carbonate
  4. dry with materialsaturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate
  5. filtrationThe reaction mixture was filtered
  6. concentrationconcentrated at reduced pressure
  7. customto give an oil that
  8. customwas purified by flash column chromatography (silica gel, 15 to 25% ethyl acetate/hexanes)
  9. customto give 1-4 and its 2 isomer

Sources & evidence

ORD record
ord-37ac060b518c4f7a8b14c5df320cc9c6
Source dataset
uspto-grants-2002_07
Patent number
US06413955B1

Reaction notes

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