(+)-L-Leucine methyl ester → HCID 2752558, compound

HRID 339486Notes

Reaction equation

HRID 339486 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH2:20][C@H:21]([C:26]([O:28][CH3:29])=[O:27])[CH2:22][CH:23]([CH3:25])[CH3:24].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:16]([O:15][C:13]([NH:1][CH:2]([CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[C:10]([NH:20][CH:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:26]([O:28][CH3:29])=[O:27])=[O:12])=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 5

HCID 65105(+)-L-Leucine methyl esterHCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 2752558HCID 2752558, compoundYield 83.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Boc-Phe-OH (2 g, 13.77 mmol), H-Leu-OMe (11 g, 41.32 mmol), HOBt (5.58 g, 41.32 mmol), and HBTU (15.67 g, 41.32 mmol) were dissolved in DMF (69 mL) and then DIPEA (7.2 mL, 41.32 mmol) was added under argon. The reaction was stirred for 8 hrs at room temperature. The reaction was extracted by EtOAc and wash with 5% NaHSO3, sat. NaHCO3 and brine. The organic layer was dried over Na2SO4, and concentrated by rotary evaporation. The crude was purified by chromatography (silica, 4/1: Hexane/EtOAc, Rf=0.3) to give methyl 2-(2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoylamino)-4-methylpentanoate as white solid (4.5 g, 8%).

Workup

  1. extractionThe reaction was extracted by EtOAc
  2. washwash with 5% NaHSO3, sat. NaHCO3 and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated by rotary evaporation
  5. customThe crude was purified by chromatography (silica, 4/1: Hexane/EtOAc, Rf=0.3)

Sources & evidence

ORD record
ord-05f93802438047d095fbc352b48933c1
Source dataset
uspto-grants-2014_11
Patent number
US08895497B2

Reaction notes

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