4-Methylmorpholine → N-[N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanyl]-3-mercapto-D-valine, methyl ester

HRID 1586888Notes

Reaction equation

HRID 1586888 reaction equation
[C:1]([NH:8][C@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[CH3:36][O:37][C:38](=[O:45])[C@@H:39]([C:41]([SH:44])([CH3:43])[CH3:42])[NH2:40]>C(Cl)Cl.C(OCC)(=O)C>[CH3:7][C:4]([CH3:5])([O:3][C:1]([NH:8][C@H:9]([C:17]([NH:40][C@@H:39]([C:38]([O:37][CH3:36])=[O:45])[C:41]([SH:44])([CH3:43])[CH3:42])=[O:19])[CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:2])[CH3:6]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 12278508Methyl 3-mercapto-D-valinate hydrochloride

Product 1

HCID 131717961N-[N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanyl]-3-mercapto-D-valine, methyl esterYield 91%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of Nα -Boc-phenylalanine (10.0 in 50 mL of methylene chloride (CH2Cl2) was cooled to -78° C. under an argon atmosphere. To this magnetically-stirred solution was added N-methylmorpholine (NMM) (3.8 g, 37.7 mmol) and isobutylchloroformate (IBCF) (5.15 g, 37.7 mmol). The reaction was allowed to slowly warm to 0° C., and then was maintained at this temperature for 45 minutes. The mixture was then recooled to -78° C., and treated with 3.8 g (37.7 mmol) of NMM and 7.5 g (37.7 mmol) of D-penicillamine methylester hydrochloride. After the reaction had warmed to room temperature and was stirred for 18 hours, it was diluted with 600 mL of ethyl acetate (EtOAc) and washed with 3×175 mL of 0.5 N potassium bisulfate (KHSO4) and 150 mL of a saturated aqueous sodium chloride solution (brine). The organic solution was then dried over anhydrous sodium sulfate (Na2SO 4), filtered, and stripped of all solvent under reduced pressure. The white solid residue title product was obtained in 91% yield (14.07 g).

Workup

  1. temperaturewas maintained at this temperature for 45 minutes
  2. customwas then recooled to -78° C.
  3. temperatureAfter the reaction had warmed to room temperature
  4. washwashed with 3×175 mL of 0.5 N potassium bisulfate (KHSO4) and 150 mL of a saturated aqueous sodium chloride solution (brine)
  5. dry with materialThe organic solution was then dried over anhydrous sodium sulfate (Na2SO 4)
  6. filtrationfiltered

Sources & evidence

ORD record
ord-7a1642a2fa844253988f47760ca6ae10
Source dataset
uspto-grants-1993_06
Patent number
US05216124

Reaction notes

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