Sodium hydride → (Z)-Methyl 2-(benzyloxycarbonylamino)-3-(4-(tert-butoxycarbonylamino)pyridin-3-yl)acrylate

HRID 901209

Reaction equation

HRID 901209 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]([NH:13][CH:14](P(OCC)(OCC)=O)[C:15]([O:17][CH3:18])=[O:16])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:27]([C:29]1[CH:30]=[N:31][CH:32]=[CH:33][C:34]=1[NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=O>C1COCC1>[CH2:3]([O:10][C:11]([NH:13]/[C:14](=[CH:27]\[C:29]1[CH:30]=[N:31][CH:32]=[CH:33][C:34]=1[NH:35][C:36]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:42])/[C:15]([O:17][CH3:18])=[O:16])=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 819566tert-Butyl (3-formylpyridin-4-yl)carbamateHCID 11068333Methyl 2-(((benzyloxy)carbonyl)amino)-2-(diethyl phosphono)acetate

Product 1

HCID 58670141(Z)-Methyl 2-(benzyloxycarbonylamino)-3-(4-(tert-butoxycarbonylamino)pyridin-3-yl)acrylateYield 58.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a slurry of 60% of sodium hydride (224 mg, 5.6 mmol) in THF (10 mL) at 0° C. was added 1A (1.72 g, 4.8 mmol) in several portions over 10 min. The reaction mixture was then brought to RT for 20 min, then cooled again at 0° C. A suspension of tert-butyl 3-formylpyridin-4-ylcarbamate (889 mg, 4 mmol) in THF (10 mL) was added over 10 min at 0° C., then the reaction was warmed up to RT. After stirring for 20 min, the reaction was quenched with water (40 mL). The aqueous layer was extracted with EtOAc (50 mL×3). The combined EtOAc extracts were dried (Na2SO4), filtered and concentrated. The resulting residue was purified by silica gel (40 g) column chromatography eluting with a gradient of EtOAc (20-100%) in hexane to give the title compound as an white foam (1 g, 58%). LC/MS (method A): retention time=2.65 min, (M+H)+=428.

Workup

  1. additionwas added over 10 min at 0° C.
  2. temperaturethe reaction was warmed up to RT
  3. customthe reaction was quenched with water (40 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (50 mL×3)
  5. dry with materialThe combined EtOAc extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by silica gel (40 g) column chromatography
  9. washeluting with a gradient of EtOAc (20-100%) in hexane

Sources & evidence

ORD record
ord-f4d0e91ed51d4442bb21ef38fc7cc279
Source dataset
uspto-grants-2008_04
Patent number
US07361766B2

Linked notes

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