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

HRID 990336Notes

Reaction equation

HRID 990336 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:17])[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.Cl.[F:52][C:53]1[CH:58]=[CH:57][C:56]([CH:59]([C:64]2[CH:69]=[CH:68][C:67]([F:70])=[CH:66][CH:65]=2)[CH2:60][CH2:61][CH2:62][NH2:63])=[CH:55][CH:54]=1>CN(C=O)C.C(OCC)C>[C:1]([O:5][C:6](=[O:7])[N:8]([C@H:9]([C:14](=[O:16])[NH:63][CH2:62][CH2:61][CH2:60][CH:59]([C:56]1[CH:55]=[CH:54][C:53]([F:52])=[CH:58][CH:57]=1)[C:64]1[CH:69]=[CH:68][C:67]([F:70])=[CH:66][CH:65]=1)[CH2:10][CH:11]([CH3:12])[CH3:13])[CH3:17])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7010555(2S)-2-{[(tert-butoxy)carbonyl](methyl)amino}-4-methylpentanoic acidHCID 18418679HCID 18418679, compound

Product 1

HCID 10553025(S)-{1-[4,4-Bis-(4-fluoro-phenyl)-butylcarbamoyl]-3-methyl-butyl}-methyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-Butoxycarbonyl-N-methyl-L-leucine (0.42 g, 1.7 mmol, Bachem Inc., Torrance, Calif.) was dissolved in dry DMF (5 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (0.90 mL, 5.2 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.66 g, 1.7 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (0.51 g, 1.7 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 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine, and was dried over Na2SO4. Concentration in vacuo followed by drying under vacuum afforded the crude desired product which was used in the subsequent reaction without further purification.

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 5% 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-cbb43b9399a1469ab55ef64c275b33ee
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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