Ethyl Acetate → (betaS)-N-(tert-Butoxycarbonyl)-4-fluoro-beta-methyl-L-phenylalanyl-L-prolinamide

HRID 970208Notes

Reaction equation

HRID 970208 reaction equation
[N:1]([C@@H:4]([C@H:8]([C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)[CH3:9])[C:5]([OH:7])=O)=[N+]=[N-].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=C[CH:31]=[CH:32][C:27]=2N=N1.ON1C2N=CC=CC=2N=N1.[NH:51]1[CH2:58][CH2:57][CH2:56][C@H:52]1[C:53]([NH2:55])=[O:54].[CH3:59]CN(C(C)C)C(C)C.[C:68]([O:71]CC)(=[O:70])C>CN(C)C=O>[C:32]([O:71][C:68]([NH:1][C@H:4]([C:5]([N:51]1[CH2:58][CH2:57][CH2:56][C@H:52]1[C:53]([NH2:55])=[O:54])=[O:7])[C@@H:8]([CH3:9])[C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)=[O:70])([CH3:31])([CH3:27])[CH3:59]

Participants

8

Reactant 6

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 111306L-ProlinamideHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 86605120(2S,3S)-2-Azido-3-(4-fluorophenyl)butanoic acid

Product 1

HCID 69417947(betaS)-N-(tert-Butoxycarbonyl)-4-fluoro-beta-methyl-L-phenylalanyl-L-prolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (2S,3S)-2-azido-3-(4-fluorophenyl)butanoic acid Example 1, Step D, 91.8 mg, 0.309 mmol) in anhydrous N,N-dimethylformamide (DMF, 1.5 mL) was added [O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) (HATU, 141 mg, 0.371 mmol), 1-hydroxy-7-azabenzotriazole (HOAT, 50.5 mg, 0.371 mmol), L-prolinamide (38.8 mg, 0.340 mmol) and N,N′-diisopropylethylamine (0.135 mL, 0.773 mmol). After stirring at room temperature for 16 h, the reaction was diluted with ethyl acetate. The organic phase was washed sequentially with water, saturated aqueous sodium bicarbonate solution and brine, dried (magnesium sulfate), and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography (silica, ethyl acetate eluant) to afford the title compound.

Workup

  1. washThe organic phase was washed sequentially with water, saturated aqueous sodium bicarbonate solution and brine
  2. dry with materialdried (magnesium sulfate)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by preparative thin layer chromatography (silica, ethyl acetate eluant)

Sources & evidence

ORD record
ord-70a22c020e3d41a68c543892ecdf3029
Source dataset
uspto-grants-2007_12
Patent number
US07309714B2

Reaction notes

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