Leucine, N-carboxy-, N-benzyl ester, L- → N2-[(benzyloxy)carbonyl)-N1-[(3S)-2-oxotetrahydrofuran-3-yl]-L-leucinamide

HRID 237344Notes

Reaction equation

HRID 237344 reaction equation
[C:1]([NH:11][C@H:12]([C:17]([OH:19])=O)[CH2:13][CH:14]([CH3:16])[CH3:15])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].Br.[NH2:21][C@H:22]1[CH2:27][CH2:26][O:25][C:23]1=[O:24].C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=N.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C.O>[CH2:4]([O:3][C:1]([NH:11][C@H:12]([C:17]([NH:21][C@H:22]1[CH2:27][CH2:26][O:25][C:23]1=[O:24])=[O:19])[CH2:13][CH:14]([CH3:15])[CH3:16])=[O:2])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

8

Reactant 5

HCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 162131383S-3-Aminodihydrofuran-2(3H)-one hydrobromideHCID 21899179Dimethylaminopropyl carbodiimide hydrochloride

Product 1

HCID 22859269N2-[(benzyloxy)carbonyl)-N1-[(3S)-2-oxotetrahydrofuran-3-yl]-L-leucinamideYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
20 °C

Procedure

3.51 g (13.25 mmol) of Cbz-L-Leucine, 2.41 g (1 eq.) of (S)-2-amino-4-butyrolactone hydrobromide, 1.97 g of HOBT (1.1 eq.) and 5.59 g (2.2 eq.) of 1-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) are dissolved in 60 ml of anhydrous DMF, then 7.64 ml of (3.3 eq.) of N,N-diisopropylethylamine is added. The reaction mixture is stirred for 15 hours at 20° C. before being poured into 200 ml of a 1/1 mixture of ethyl acetate/water. After stirring and decantation, the organic solution is washed successively with 100 ml of a saturated solution of NaHCO3, 50 ml of water, 100 ml of a 1M solution of citric acid and finally 100 ml of a solution of salt water. The organic phase is dried over sodium sulphate, filtered and concentrated to dryness under vacuum. The oil obtained is washed using isopentane and then crystallized from a dichloromethane/isopentane mixture. A white solid is obtained with a yield of 68%. Melting point: 130-131° C.

Workup

  1. stirringAfter stirring
  2. washdecantation, the organic solution is washed successively with 100 ml of a saturated solution of NaHCO3, 50 ml of water, 100 ml of a 1M solution of citric acid and finally 100 ml of a solution of salt water
  3. dry with materialThe organic phase is dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under vacuum
  6. customThe oil obtained
  7. washis washed
  8. customcrystallized from a dichloromethane/isopentane mixture
  9. customA white solid is obtained with a yield of 68%

Sources & evidence

ORD record
ord-5ddcaf40e449433e8031b8d517cab0d6
Source dataset
uspto-grants-2014_02
Patent number
US08642591B2

Reaction notes

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