4-Methylmorpholine → N-[N-(t-butoxycarbonyl)-L-seryl]-L-cysteine methyl ester

HRID 375716Notes

Reaction equation

HRID 375716 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:9])[C@H:5]([CH2:7][SH:8])[NH2:6].[C:10]([O:14][C:15]([NH:17][C@H:18]([C:21](O)=[O:22])[CH2:19][OH:20])=[O:16])([CH3:13])([CH3:12])[CH3:11].CN1CCOCC1>C(#N)C>[CH3:2][O:3][C:4](=[O:9])[C@H:5]([CH2:7][SH:8])[NH:6][C:19](=[O:20])[C@H:18]([CH2:21][OH:22])[NH:17][C:15]([O:14][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:16]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 98766N-[tert-butoxycarbonyl]-L-serineHCID 2733208L-Cysteine, methyl ester, hydrochloride

Product 1

HCID 11727022N-[N-(t-butoxycarbonyl)-L-seryl]-L-cysteine methyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 17.2 g of L-cysteine methyl ester hydrochloride and 20.5 g of N-(t-butoxycarbonyl)-L-serine in 300 ml of acetonitrile was treated at 0° C. with 10.1 g of 4-methylmorpholine. To the stirred solution was added dropwise at 10° C. within 30 minutes a solution of 20.6 g N,N-dicyclohexylcarbodiimide in 300 ml of acetonitrile. After stirring the reaction mixture for 3 hours at 0° C. the precipitate formed was filtered off, and the filtrate was evaporated in vacuo. The oily residue was dissolved in 200 ml of ethyl acetate and the solution washed consecutively with 0.5N hydrochloric acid, water, 5% aqueous sodium bicarbonate solution and brine. The organic layer was dried over sodium sulfate and evaporated in vacuo. The crude product was chromatographed on silica gel using ethyl acetate/n-hexane as eluent, and the so purified product was crystallized from diethyl ether/n-hexane to give N-[N-(t-butoxycarbonyl)-L-seryl]-L-cysteine methyl ester as white crystals with mp 72°-74° C.

Workup

  1. customformed
  2. filtrationwas filtered off
  3. customthe filtrate was evaporated in vacuo
  4. dissolutionThe oily residue was dissolved in 200 ml of ethyl acetate
  5. washthe solution washed consecutively with 0.5N hydrochloric acid, water, 5% aqueous sodium bicarbonate solution and brine
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customevaporated in vacuo
  8. customThe crude product was chromatographed on silica gel
  9. customthe so purified product was crystallized from diethyl ether/n-hexane

Sources & evidence

ORD record
ord-3f8f567845de46428e71fe5c3cfbd133
Source dataset
uspto-grants-1996_01
Patent number
US05486466

Reaction notes

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