Benzyl Alcohol → Methyl 3-(((benzyloxy)carbonyl)amino)-3-methylbutanoate

HRID 1903

Reaction equation

HRID 1903 reaction equation
[CH3:1][O:2][C:3](=[O:11])[CH2:4][C:5]([CH3:10])([CH3:9])C(O)=O.C([N:14]([CH2:17]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:26])C=CC=CC=1.[CH2:36]([OH:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1C=CC=CC=1>[CH2:36]([O:43][C:17]([NH:14][C:5]([CH3:9])([CH3:10])[CH2:4][C:3]([O:2][CH3:1])=[O:11])=[O:26])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 126021764-Methoxy-2,2-dimethyl-4-oxobutanoic acid

Product 1

HCID 15042554Methyl 3-(((benzyloxy)carbonyl)amino)-3-methylbutanoateYield 75.1%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To 14.7 g (91.8 mmol) of 2,2-dimethylbutanedioic acid-4-methyl ester in 150 mL of benzene was added 13 mL of triethylamine (9.4 g, 93 mmol) followed by 21.8 mL of diphenylphosphoryl azide (27.8 g, 101 mmol). The mixture was heated under nitrogen at reflux for 45 minutes then 19 mL (19.9 g, 184 mmol) of benzyl alcohol was added and refluxing continued for 16 hours. The mixture was cooled, filtered and the filtrate concentrated to a minimum volume under vacuum. The residue was redissolved in 250 mL of ethyl acetate, washed with water, saturated aqueous sodium bicarbonate (2×) and brine. The organic layer was removed, dried over magnesium sulfate, filtered and the filtrate concentrated to a minimum volume under vacuum. The crude product was purified by medium pressure liquid chromatography on silica, eluting with hexane/ethyl acetate (4:1), to afford 18.27 g (68.9 mmol, 75%) of the product.

Workup

  1. temperatureThe mixture was heated under nitrogen
  2. temperatureat reflux for 45 minutes
  3. temperaturerefluxing
  4. temperatureThe mixture was cooled
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated to a minimum volume under vacuum
  7. dissolutionThe residue was redissolved in 250 mL of ethyl acetate
  8. washwashed with water, saturated aqueous sodium bicarbonate (2×) and brine
  9. customThe organic layer was removed
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated to a minimum volume under vacuum
  13. customThe crude product was purified by medium pressure liquid chromatography on silica
  14. washeluting with hexane/ethyl acetate (4:1)

Sources & evidence

ORD record
ord-4b176a6bf0704d8d9641aa04cf712b48
Source dataset
uspto-grants-1998_03
Patent number
US05726319

Linked notes

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