Methyl chloroformate → N-Benzyloxy-t-butoxycarbonyl-threonine amide

HRID 2165274Notes

Reaction equation

HRID 2165274 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]([OH:15])=O)[C@@H:10]([CH3:12])[OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)CC1C=CC=CC=1.ClC(OC)=O.[C:31]1([CH2:37][O:38][NH2:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]([NH:39][O:38][CH2:37][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:15])[C@@H:10]([CH3:12])[OH:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 7681N,N-DimethylbenzylamineHCID 102313O-BenzylhydroxylamineHCID 2724766N-tert-Butoxycarbonyl-L-threonine

Product 1

HCID 18598709N-Benzyloxy-t-butoxycarbonyl-threonine amideYield 74.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
-10 °C

Procedure

N-(t-Butyloxycarbonyl)-L-threonine (82.2 g) was dissolved in 1 liter of ethyl acetate and 40.5 g of dimethyl (phenylmethyl)amine was added. After stirring for 10 minutes the mixture was cooled to -10° C. and 31.05 g of methyl chloroformate were added dropwise. The mixture was stirred for 30 minutes at -10° C., after which a solution of 40.65 g of (phenylmethoxy)amine in 300 ml of ethyl acetate was added at -10° C. The temperature was then permitted to rise to 5° C. during a 90 minute period. The reaction mixture was evaporated in vacuo and redissolved in 1 liter of ethyl acetate the insoluble material was filtered off and the filtrate washed, with cooling, with water, dilute hydrochloric acid, (pH of aqueous phase not less than 2.5), sodium bicarbonate solution and brine. After drying (MgSO4) the solvent was removed in vacuo to yield an oil, which crystallized on treatment with petroleum ether, yielding 79.4 g of the title compound, melting point 87° C.

Workup

  1. stirringThe mixture was stirred for 30 minutes at -10° C.
  2. waitto rise to 5° C. during a 90 minute period
  3. customThe reaction mixture was evaporated in vacuo
  4. dissolutionredissolved in 1 liter of ethyl acetate the insoluble material
  5. filtrationwas filtered off
  6. washthe filtrate washed
  7. temperaturewith cooling, with water, dilute hydrochloric acid
  8. dry with materialAfter drying (MgSO4) the solvent
  9. customwas removed in vacuo
  10. customto yield an oil, which
  11. customcrystallized on treatment with petroleum ether

Sources & evidence

ORD record
ord-2c33ab51ab1b4839a72ebc20fd24a981
Source dataset
uspto-grants-1990_07
Patent number
US04939253

Reaction notes

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