Diisopropylethylamine → HCID 53810669, compound

HRID 990366Notes

Reaction equation

HRID 990366 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.[F:49][C:50]1[CH:55]=[CH:54][C:53]([CH:56]([C:63]2[CH:68]=[CH:67][C:66]([F:69])=[CH:65][CH:64]=2)[N:57]2[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)=[CH:52][CH:51]=1>CN(C=O)C.C(OCC)C>[F:69][C:66]1[CH:65]=[CH:64][C:63]([CH:56]([C:53]2[CH:54]=[CH:55][C:50]([F:49])=[CH:51][CH:52]=2)[N:57]2[CH2:58][CH2:59][N:60]([C:6](=[O:8])[C@@H:5]([N:9]3[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]3)[CH2:4][CH:3]([CH3:2])[CH3:15])[CH2:61][CH2:62]2)=[CH:68][CH:67]=1

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)2×HCID 70071127HCID 70071127, compound

Product 1

HCID 53810669HCID 53810669, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of (S)-4-methyl-2-piperidin-1-yl-pentanoic acid monohydrobromide (0.28 g, 1.0 mmol, Example 22, Step A) and N,N-diisopropylethylamine (0.52 mL, 3.0 mmol) in dry DMF (6 mL) was added solid O-benzotriazol-1-yl -N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.39 g, 0.99 mmol) under nitrogen atmosphere at 0° C. The resulting reaction mixture, which became a clear solution after addition of O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate, was stirred at that temperature for 20 minutes; solid 1-bis(4-fluorophenyl)methyl piperazine (0.29 g, 1.0 mmol) was then added. After additional 3 hours stirring while the reaction mixture was allowed to slowly warm up to ambient temperature, reaction mixture was mixed with 100 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×100 mL), brine (2×100 mL), and dried over MgSO4. The solution was concentrated in vacuo affording an amber oil. The crude product was further purified by flash chromatography (20:80:1 EtOAc:hexane:MeOH) to provide 0.37 g (79%) of the pure titled compound as a white foam. APCI-MS m/z 470.3 (MH+).

Workup

  1. customThe resulting reaction mixture, which
  2. stirringAfter additional 3 hours stirring while the reaction mixture
  3. customreaction mixture
  4. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×100 mL), brine (2×100 mL)
  5. dry with materialdried over MgSO4
  6. concentrationThe solution was concentrated in vacuo
  7. customaffording an amber oil
  8. customThe crude product was further purified by flash chromatography (20:80:1 EtOAc:hexane:MeOH)

Sources & evidence

ORD record
ord-0a5f4d90687249fbb49699a83f124d76
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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