4-Methylmorpholine → N-benzyloxycarbonyl-L-leucyl-L-leucine t-butyl ester

HRID 133010Notes

Reaction equation

HRID 133010 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:17]([OH:19])=O)[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:21]([O:25][C:26](=[O:33])[C@H:27]([CH2:29][CH:30]([CH3:32])[CH3:31])[NH2:28])([CH3:24])([CH3:23])[CH3:22].ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.CN1CCOCC1>C(Cl)Cl>[C:21]([O:25][C:26](=[O:33])[C@H:27]([CH2:29][CH:30]([CH3:31])[CH3:32])[NH:28][C:17](=[O:19])[C@H:12]([CH2:13][CH:14]([CH3:15])[CH3:16])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])([CH3:24])([CH3:23])[CH3:22]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 757711-HydroxybenzotriazoleHCID 12451443tert-butyl (2S)-2-amino-4-methylpentanoate hydrochloride

Product 1

HCID 60004050N-benzyloxycarbonyl-L-leucyl-L-leucine t-butyl esterYield 99.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under atmosphere of argon, to a solution of N-benzyloxycarbonylleucine (26.5 g) and leucine t-butyl ester hydrochloride (22.4 g) in methylene chloride (20.0 ml.) were added 1-hydroxybenzotriazole (HOBt) (14.2 g) and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) hydrochloride (20.1 g) at 0° C. Thereto was added N-methylmorpholine (11.5 ml) over a period of 5 minutes and the mixture was stirred for 20 hours at room temperature. The reaction solution was concentrated and to the residue were added ice-water and ethyl acetate. In order to dissolve HOBt that appeared, was added sodium bicarbonate. The aqueous layer was extracted with ethyl acetate and combined organic layer was washed with 10% aqueous solution of citric acid, a saturated aqueous solution of sodium bicarbonate and saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and was concentrated to give the title compound (43.2 g) having the following physical data.

Workup

  1. concentrationThe reaction solution was concentrated and to the residue
  2. additionwere added ice-water and ethyl acetate
  3. dissolutionIn order to dissolve HOBt
  4. additionwas added sodium bicarbonate
  5. extractionThe aqueous layer was extracted with ethyl acetate and combined organic layer
  6. washwas washed with 10% aqueous solution of citric acid
  7. dry with materiala saturated aqueous solution of sodium bicarbonate and saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  8. concentrationwas concentrated

Sources & evidence

ORD record
ord-cbd0bdc1d1a141ffb0f68f051d9fe1fa
Source dataset
uspto-grants-2008_06
Patent number
US07390804B2

Reaction notes

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