Reaction #1771987

Reaction equation

methyliodide

lithium hexamethyldisilazide

tert-butyl N-tert-butoxycarbonylpyroglutamate

→

Boc-PyroGlu(4-methyl)-OtBu

Yield 88.0%

Tert-Butyl N-tert-butoxycarbonyl-4-methyl-L-pyroglutamate

Yield 88.0%

Solvents

THF

THF

Conditions

Workup

1. 1
   workup.WAITAfter an additional 2 hours at −78° C.
2. 2
   Otherthe cooling bath was removed
3. 3
   workup.ADDITION50% saturated aqueous ammonium chloride (200 mL) was added
4. 4
   Extractionextracted with ether (3×200 mL)
5. 5
   WashThe combined organic layers were washed with brine (200 mL)
6. 6
   Dryingdried (Na2SO4)
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated
9. 9
   OtherThe residue was chromatographed with 1:1 ethylacetate/hexanes

Procedure

To a solution of tert-butyl N-tert-butoxycarbonylpyroglutamate (11.5 g, 40 mmol) in THF (200 mL) stirring at −78° C., was added a 1M solution of lithium hexamethyldisilazide in THF (42 mL, 42 mmol) dropwise over 5 minutes. After 30 minutes, methyliodide (3.11 mL, 50 mmol) was added. After an additional 2 hours at −78° C., the cooling bath was removed and 50% saturated aqueous ammonium chloride (200 mL) was added. The solution was stirred for 20 minutes, then extracted with ether (3×200 mL). The combined organic layers were washed with brine (200 mL), dried (Na2SO4), filtered and concentrated. The residue was chromatographed with 1:1 ethylacetate/hexanes to give Boc-PyroGlu(4-methyl)-OtBu (10.6 grams, 35.4 mmol, 88%) as a mixture of isomers (2:1 cis to trans).

Source