Sodium hydride → (Z)-Methyl 2-(benzyloxycarbonylamino)-3-(2-(tert-butoxycarbonyl amino)-5-phenylpyridin-3-yl)acrylate

HRID 2221088Notes

Reaction equation

HRID 2221088 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[C:30]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[N:31][CH:32]=[C:33]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:34]=1)=O>C1COCC1>[CH2:3]([O:10][C:11]([NH:13]/[C:14](=[CH:27]\[C:29]1[C:30]([NH:41][C:42]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:48])=[N:31][CH:32]=[C:33]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:34]=1)/[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 11068333Methyl 2-(((benzyloxy)carbonyl)amino)-2-(diethyl phosphono)acetateHCID 58671547tert-Butyl 3-formyl-5-phenylpyridin-2-ylcarbamate

Product 1

HCID 58671540(Z)-Methyl 2-(benzyloxycarbonylamino)-3-(2-(tert-butoxycarbonyl amino)-5-phenylpyridin-3-yl)acrylateYield 44.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a slurry of 60% of sodium hydride (156 mg, 3.90 mmol) in THF (8 niL) at 0° C. was added 1A (1.2 g, 3.34 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 1D (830 mg, 2.78 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 (30 mL). The aqueous layer was extracted with EtOAc (50 mL×2). The combined organics were dried (Na2SO4), filtered and concentrated. The resulting residue was triturated with CH2Cl2-hexanes to give the title compound (620 mg). The mother liquid was concentrated and the resulting residue was purified by silica gel (110 g) column chromatography eluting with a gradient of EtOAc (0-60%) in hexane to give additional 130 mg of the title compound (total 750 mg, 54%) as an off-white solid. LC/MS (method A): retention time=3.40 min, (M+H)+=504.

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 (30 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (50 mL×2)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was triturated with CH2Cl2-hexanes

Sources & evidence

ORD record
ord-78d8ec4cf08242dd8004c61a2b62b7c1
Source dataset
uspto-grants-2008_05
Patent number
US07368458B2

Reaction notes

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