Hydrochloric Acid → Benzhydryl 2-{4-[2-(acetylamino)-3-oxo-3-({5-oxo-5-[2-(trimethylsilyl)ethoxy]pentyl}amino)propyl][tert-butoxy(oxo)acetyl]-2-ethylanilino}benzoate

HRID 488641Notes

Reaction equation

HRID 488641 reaction equation
C(O[C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])=[O:14])=[O:7])(C)(C)C.Cl.[C:23]([NH:26][C@H:27](C(O)=O)[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]([C:58](=[O:66])[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[C:42]([O:44][CH:45]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[O:43])=[C:31]([CH2:67][CH3:68])[CH:30]=1)(=[O:25])[CH3:24].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>O1CCOCC1.CN(C)C=O.C(OCC)(=O)C>[C:23]([NH:26][CH:27]([C:6](=[O:7])[NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13](=[O:14])[O:15][CH2:16][CH2:17][Si:18]([CH3:19])([CH3:20])[CH3:21])[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([N:35]([C:58](=[O:66])[C:59]([O:61][C:62]([CH3:64])([CH3:65])[CH3:63])=[O:60])[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[C:42]([O:44][CH:45]([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)[C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[O:43])=[C:31]([CH2:67][CH3:68])[CH:30]=1)(=[O:25])[CH3:24]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 222719852-(Trimethylsilyl)ethyl 5-[(tert-butoxycarbonyl)amino]pentanoateHCID 69803046N-acetyl-4-{2-[(benzhydryloxy)carbonyl][tert-butoxy(oxo)acetyl]anilino}-3-ethylphenylalanine

Product 1

HCID 22271935Benzhydryl 2-{4-[2-(acetylamino)-3-oxo-3-({5-oxo-5-[2-(trimethylsilyl)ethoxy]pentyl}amino)propyl][tert-butoxy(oxo)acetyl]-2-ethylanilino}benzoateYield 55.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

2-(trimethylsilyl)ethyl 5-[(tert-butoxycarbonyl)amino]pentanoate (317 mg, 1.0 mmol) was treated with 4N HCl in dioxane at room temperature for 30 minutes, then concentrated under reduced pressure. The residue (665 mg, 1.0 mmol), N-acetyl-4-{2-[(benzhydryloxy)carbonyl][tert-butoxy(oxo)acetyl]anilino}-3-ethylphenylalanine (665 mg, 1.0 mmol), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (321 mg, 1.0 mmol) and diisopropylethylamine (521 μL, 3.0 mmol) in N,N-dimethylformamide (2 mL) was stirred at ambient temperature overnight, diluted with ethyl acetate and washed with aqueous NaHCO3 (1×30 mL), brine (1×30 mL), dried (MgSO4), filtered and concentrate under reduced pressure. The residue was purified on silica gel eluting with ethyl acetate to provide of titled compound 480 mg. MS (APCI(+)) m/e 864 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. washwashed with aqueous NaHCO3 (1×30 mL), brine (1×30 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrate under reduced pressure
  6. customThe residue was purified on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-db0eaa6ec8b5485d9255cfca2330d1d4
Source dataset
uspto-grants-2005_12
Patent number
US06972340B2

Reaction notes

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