Diethyl Ether → HCID 86758549, compound

HRID 990348Notes

Reaction equation

HRID 990348 reaction equation
[CH:1]1([N:7]([CH3:16])[C@@H:8]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[ClH:26].[F:27][C:28]1[CH:33]=[CH:32][C:31]([CH:34]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)[CH2:35][CH2:36][CH2:37][NH2:38])=[CH:30][CH:29]=1.C(OCC)C>CN(C=O)C>[ClH:26].[F:27][C:28]1[CH:33]=[CH:32][C:31]([CH:34]([C:39]2[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=2)[CH2:35][CH2:36][CH2:37][NH:38][C:9](=[O:11])[C@@H:8]([N:7]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH3:16])[CH2:12][CH:13]([CH3:15])[CH3:14])=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 11401906HCID 11401906, compoundHCID 18418679HCID 18418679, compound

Product 1

HCID 86758549HCID 86758549, compoundYield 76.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-(Cyclohexyl-methyl-amino)-4-methyl-pentanoic acid (0.300 g, 1.32 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 (0.690 mL, 3.96 mmol) and solid O-benzotriazol-1-yl-N,N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.501 g, 1.32 mmol). The resulting reaction mixture was stirred at that temperature for 40 minutes; solid 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (0.393 g, 1.32 mmol) was then added. After stirring for, sequentially, 15 minutes at 0° C. and 30 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 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 0.51 g (75%) of the pure titled compound as a white foam; mp 73-83° C. APCI-MS m/z 471.4 (MH+).

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter stirring for, sequentially, 15 minutes at 0° C.
  3. custom30 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 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-1d61a42a51634b9280643aac2c7b5729
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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