Diisopropylethylamine → (S)-{1-[4,4-Bis-(4-fluoro-phenyl)-butylcarbamoyl]-3-methyl-butyl}-carbamic acid tert-butyl ester

HRID 990330Notes

Reaction equation

HRID 990330 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])=[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.C1(CCCCN)C=CC=CC=1.Cl.[F:62][C:63]1[CH:68]=[CH:67][C:66]([CH:69]([C:74]2[CH:79]=[CH:78][C:77]([F:80])=[CH:76][CH:75]=2)[CH2:70][CH2:71][CH2:72][NH2:73])=[CH:65][CH:64]=1>CN(C=O)C.C(OCC)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:14](=[O:16])[NH:73][CH2:72][CH2:71][CH2:70][CH:69]([C:66]1[CH:65]=[CH:64][C:63]([F:62])=[CH:68][CH:67]=1)[C:74]1[CH:79]=[CH:78][C:77]([F:80])=[CH:76][CH:75]=1)[CH2:10][CH:11]([CH3:12])[CH3:13])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 83242BenzenebutanamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18418679HCID 18418679, compound

Product 1

HCID 12017807(S)-{1-[4,4-Bis-(4-fluoro-phenyl)-butylcarbamoyl]-3-methyl-butyl}-carbamic acid tert-butyl esterYield 90%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl-L-leucine (0.84 g, 3.4 mmol, Bachem Inc., Torrance, Calif.) was dissolved in dry DMF (7 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (1.8 mL, 10 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.3 g, 3.4 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; benzenebutanamine, 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (1.0 g, 3.4 mmol) was then added. After additional 30 minutes stirring at 0° C., reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with 2% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine, and was dried over Na2SO4. Concentration in vacuo followed by drying under vacuum afforded 1.4 g (90%) of the pure titled compound was obtained as a white foam: mp 50-55° C. APCI-MS m/z 475.3 (MH+).

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter additional 30 minutes stirring at 0° C.
  3. customreaction mixture
  4. washthe resulting mixture was successively washed with 2% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine
  5. dry with materialwas dried over Na2SO4
  6. concentrationConcentration in vacuo
  7. customby drying under vacuum

Sources & evidence

ORD record
ord-afa3e9bc39d54069bac14ab6b9edaba0
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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