Sodium hydride → HCID 68478207, compound

HRID 587942Notes

Reaction equation

HRID 587942 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]([CH3:28])[CH2:11][CH2:12][C:13]1[CH:14]=[C:15]([CH:19](C(OC)=O)[C:20]([O:22][CH3:23])=[O:21])[CH:16]=[CH:17][CH:18]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>O1CCCC1.CO>[C:3]([O:7][C:8]([N:10]([CH3:28])[CH2:11][CH2:12][C:13]1[CH:14]=[C:15]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH:16]=[CH:17][CH:18]=1)=[O:9])([CH3:5])([CH3:4])[CH3:6]

Participants

5

Reactant 2

HCID 24758Sodium hydride2×HCID 68475029HCID 68475029, compound

Product 1

HCID 68478207HCID 68478207, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

To 429 μL (10.6 mmol) of methanol was slowly added 85 mg (2.1 mmol) of sodium hydride (60% dispersion in mineral oil). This mixture was then added to a separate solution of 387 mg (1.06 mmol) of dimethyl 2-(3-(2-(tert-butoxycarbonyl(methyl)amino)ethyl)phenyl)malonate in 5 mL of tetrahydrofuran. The resulting solution was refluxed for 2 h then cooled to 22° C. An additional 85 mg of NaH in 429 ml of methanol was added and the solution was again heated to reflux for about 16 h. The solvent was evaporated and the residue partitioned between saturated NH4Cl and ethyl acetate. The organic layer was washed with brine, dried (Na2SO4), filtered and evaporated. The residue was purified by flash chromatography on silica gel, eluting first with hexane and then gradually increasing to 15% ethyl acetate/hexane to give methyl 2-(3-(2-(tert-butoxycarbonyl(methyl)amino)ethyl)phenyl)acetate.

Workup

  1. temperatureThe resulting solution was refluxed for 2 h
  2. temperaturethe solution was again heated
  3. temperatureto reflux for about 16 h
  4. customThe solvent was evaporated
  5. customthe residue partitioned between saturated NH4Cl and ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by flash chromatography on silica gel
  11. washeluting first with hexane
  12. temperaturegradually increasing to 15% ethyl acetate/hexane

Sources & evidence

ORD record
ord-9c4e52f088f64f9ba7205ea87b4fae4e
Source dataset
uspto-grants-2016_01
Patent number
US09227918B2

Reaction notes

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