Leucine, N-carboxy-, N-benzyl ester, L- → N-Benzyloxycarbonyl-L-leucine-N-methylamide

HRID 1971089Notes

Reaction equation

HRID 1971089 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.CN.C[CH2:24][N:25](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[CH3:24][NH:25][C:17](=[O:19])[C@H:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10]

Participants

6

Reactant 4

HCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 6364545Methylamine hydrochloride

Product 1

HCID 14888798N-Benzyloxycarbonyl-L-leucine-N-methylamideYield 96.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-Benzyloxycarbonyl-L-leucine (1.18 g, 4.45 mmol), methylamine hydrochloride (0.60 g, 8.90 mmol) and DIEA (3.0 mL, 17.2 mmol) in DMF (40 mL) was added TBTU (1.43 g, 5.6 mmol) at 0° C. in two batches over 10 minutes. After stirring at room temperature overnight, the reaction was quenched with water (5 mL) and evaporated under vacuum. The residue was partitioned between brine and EtOAc. The organic phase was dried over anhydrous Na2SO4, filtered and evaporated to dryness. The residue was filtered through a short pad of silica gel with EtOAc to give crude product 20A (1.20 g) which was used in the next step without purification. LCMS (+ESI) m/z 301.1 [M+Na]+.

Workup

  1. customthe reaction was quenched with water (5 mL)
  2. customevaporated under vacuum
  3. customThe residue was partitioned between brine and EtOAc
  4. dry with materialThe organic phase was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. filtrationThe residue was filtered through a short pad of silica gel with EtOAc

Sources & evidence

ORD record
ord-921ec3a49aa942cd9520fc239f3ef56b
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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