L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]- → HCID 12017815, compound

HRID 990377Notes

Reaction equation

HRID 990377 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].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:53][C:54]1[CH:59]=[CH:58][C:57]([CH:60]([C:67]2[CH:72]=[CH:71][C:70]([F:73])=[CH:69][CH:68]=2)[N:61]2[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]2)=[CH:56][CH:55]=1>CN(C=O)C.C(OCC)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:17]([N:64]1[CH2:63][CH2:62][N:61]([CH:60]([C:67]2[CH:72]=[CH:71][C:70]([F:73])=[CH:69][CH:68]=2)[C:57]2[CH:56]=[CH:55][C:54]([F:53])=[CH:59][CH:58]=2)[CH2:66][CH2:65]1)=[O:19])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 81531DiisopropylethylamineHCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 12017815HCID 12017815, compoundYield 95.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-Butoxycarbonyl-L-phenylalanine (4.60 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 O-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 8.88 g (95%) of the pure titled compound as a off-white foam: mp 54-74° C. APCI-MS m/z 536.4 (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-4f5290bc56554305870e7d13493a2d65
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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