Diethyl Ether → HCID 10567950, compound

HRID 361806Notes

Reaction equation

HRID 361806 reaction equation
C[Li].[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH3:25])[C:17]2[C:22](C#N)=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CC[O:28][CH2:29][CH3:30]>>[CH2:3]([N:10]1[CH2:11][CH2:12][CH:13]([N:16]([CH3:25])[C:17]2[C:22]([C:29](=[O:28])[CH3:30])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:14][CH2:15]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

4

Reactant 3

HCID 3283Diethyl Ether2×HCID 10757058HCID 10757058, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 10567950HCID 10567950, compound

Procedure

To a flame-dried flask containing a mixture of methyllithium (1.5M in ether as complexed with lithium bromide, 5.2 ml) in anhydrous ether (5.2 ml) at -78° under nitrogen is added a solution of 1-benzyl-4-(N-methyl-N-(3-cyano-2-pyridyl)amino)piperidine (XXXIII, EXAMPLE 42, 1.2 g) in anhydrous ether (5.3 ml) over 5 min. The resulting mixture is allowed to warm up to 0° over approximately 2.25 hrs and is quenched with sulfuric acid (2N, 3.9 ml) and stirred at 20°-25° for 2 hrs. The biphasic mixture is then adjusted to pH 10-11 with aqueous sodium hydroxide (5%), diluted with ether (10 ml) and water (10 ml) and the phases are separated. The aqueous phase is extracted with additional ether (30 ml), and the combined organic phases are washed with saline (10 ml), dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and chromatographed (silica gel, 70-230 mesh, 50 g; ethyl acetate/hexane (50/50)) to give the title compound, mp=93°-94°.

Workup

  1. additionTo a flame-dried flask containing
  2. temperatureto warm up to 0° over approximately 2.25 hrs
  3. customis quenched with sulfuric acid (2N, 3.9 ml)
  4. additiondiluted with ether (10 ml) and water (10 ml)
  5. customthe phases are separated
  6. extractionThe aqueous phase is extracted with additional ether (30 ml)
  7. washthe combined organic phases are washed with saline (10 ml)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customchromatographed (silica gel, 70-230 mesh, 50 g; ethyl acetate/hexane (50/50))

Sources & evidence

ORD record
ord-be1a15a23ad64095b77039f5ad53844e
Source dataset
uspto-grants-1999_02
Patent number
US05866589

Reaction notes

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