Diisopropylethylamine → HCID 54172469, compound

HRID 990376Notes

Reaction equation

HRID 990376 reaction equation
O.[C:2]([O:6][C:7]([NH:9][C@H:10]([C:15]([OH:17])=O)[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8])([CH3:5])([CH3:4])[CH3:3].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:51][C:52]1[CH:57]=[CH:56][C:55]([CH:58]([C:65]2[CH:70]=[CH:69][C:68]([F:71])=[CH:67][CH:66]=2)[N:59]2[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]2)=[CH:54][CH:53]=1>CN(C=O)C.C(OCC)C>[C:2]([O:6][C:7](=[O:8])[NH:9][C@H:10]([C:15]([N:62]1[CH2:61][CH2:60][N:59]([CH:58]([C:65]2[CH:70]=[CH:69][C:68]([F:71])=[CH:67][CH:66]=2)[C:55]2[CH:54]=[CH:53][C:52]([F:51])=[CH:57][CH:56]=2)[CH2:64][CH2:63]1)=[O:17])[CH2:11][CH:12]([CH3:13])[CH3:14])([CH3:3])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12373896N-Boc-L-Leucine Hydrate

Product 1

HCID 54172469HCID 54172469, compoundYield 94.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-Butoxycarbonyl-L-leucine monohydrate (4.32 g, 17.3 mmol, Bachem Inc., Torrance, Calif.) was dissolved in dry DMF (33 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (6.04 mL, 34.7 mmol) and solid -benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (6.58 g, 17.4 mmol). The resulting reaction mixture was stirred at that temperature for 35 minutes; solid 1-bis(4-fluorophenyl)methyl piperazine (5.00 g, 17.3 mmol) was then added. After stirring for, sequentially, 15 minutes at 0° C. and 30 minutes at ambient temperature, reaction mixture was mixed with 120 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×120 mL), brine (2×120 mL), and was dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The crude product was further purified by flash chromatography (30% EtOAc in hexanes) to provide 8.23 g (94%) of the pure titled compound as a off-white foam: mp 59-66° C. APCI-MS m/z 502.4 (MH+).

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter stirring for, sequentially, 15 minutes at 0° C.
  3. custom30 minutes at ambient temperature, reaction mixture
  4. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×120 mL), brine (2×120 mL)
  5. dry with materialwas dried over Na2SO4
  6. concentrationThe solution was concentrated in vacuo
  7. customaffording a viscous oil
  8. customThe crude product was further purified by flash chromatography (30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3995d4d7429e4cb8b04a97f546312fd7
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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