Diisopropylethylamine → HCID 54429525, compound

HRID 990349Notes

Reaction equation

HRID 990349 reaction equation
Br.[CH3:2][CH:3]([CH3:15])[CH2:4][C@H:5]([N:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[C:6]([OH:8])=O.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:50][C:51]1[CH:56]=[CH:55][C:54]([CH:57]([C:62]2[CH:67]=[CH:66][C:65]([F:68])=[CH:64][CH:63]=2)[CH2:58][CH2:59][CH2:60][NH2:61])=[CH:53][CH:52]=1>CN(C=O)C.C(OCC)C>[F:50][C:51]1[CH:56]=[CH:55][C:54]([CH:57]([C:62]2[CH:63]=[CH:64][C:65]([F:68])=[CH:66][CH:67]=2)[CH2:58][CH2:59][CH2:60][NH:61][C:6](=[O:8])[C@@H:5]([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH2:4][CH:3]([CH3:2])[CH3:15])=[CH:53][CH:52]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18418679HCID 18418679, compoundHCID 70071127HCID 70071127, compound

Product 1

HCID 54429525HCID 54429525, compoundYield 59.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(S)-4-Methyl-2-piperidin-1-yl-pentanoic acid monohydrobromide (0.300 g, 1.51 mmol) was dissolved in dry DMF (4 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (0.787 mL, 4.52 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.571 g, 1.51 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; solid 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (0.448 g, 1.51 mmol) was then added. After stirring for, sequentially, 10 minutes at 0° C. and 45 minutes at ambient temperature, reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL), and was dried over Na2SO4. The solution was concentrated in vacuo affording an viscous oil. The crude product was further purified by flash chromatography (50% EtOAc in hexane) and treated with ethereal HCl. Subsequent concentration in vacuo and drying under vacuum provided 0.4 g (54%) of the pure titled compound as a white foam; mp 52-70° C. APCI-MS m/z 443.4 (MH+).

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter stirring for, sequentially, 10 minutes at 0° C.
  3. custom45 minutes at ambient temperature, reaction mixture
  4. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL)
  5. dry with materialwas dried over Na2SO4
  6. concentrationThe solution was concentrated in vacuo
  7. customaffording an viscous oil
  8. customThe crude product was further purified by flash chromatography (50% EtOAc in hexane)
  9. additiontreated with ethereal HCl
  10. concentrationSubsequent concentration in vacuo
  11. customdrying under vacuum

Sources & evidence

ORD record
ord-7f54f117150640609ec6b444042b3d9e
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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