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

HRID 2375165Notes

Reaction equation

HRID 2375165 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=NCC.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 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 162131383S-3-Aminodihydrofuran-2(3H)-one hydrobromide

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)-3-ethylcarbodiimide hydrochloride (EDC) is dissolved in 60 ml of anhydrous DMF then 7.64 ml (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-f9487fe7c7d141cb8001c53bdf0e64e2
Source dataset
uspto-grants-2008_12
Patent number
US07465721B2

Reaction notes

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