Diethyl Ether → HCID 54162779, compound

HRID 990351Notes

Reaction equation

HRID 990351 reaction equation
C(N(CC)[CH:5]([CH3:7])[CH3:6])(C)C.F[P-](F)(F)(F)(F)F.[N:17]1(OC(N(C)C)=[N+](C)C)[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2N=N1.Cl.[F:35][C:36]1[CH:41]=[CH:40][C:39]([CH:42]([C:47]2[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=2)[CH2:43][CH2:44][CH2:45][NH2:46])=[CH:38][CH:37]=1.C([O:56][CH2:57][CH3:58])C.C[N:60]([CH:62]=[O:63])C>>[F:35][C:36]1[CH:41]=[CH:40][C:39]([CH:42]([C:47]2[CH:48]=[CH:49][C:50]([F:53])=[CH:51][CH:52]=2)[CH2:43][CH2:44][CH2:45][NH:46][C:57]([C@@H:58]([NH:60][C:62]([N:17]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:20]2)=[O:63])[CH:5]([CH3:6])[CH3:7])=[O:56])=[CH:38][CH:37]=1

Participants

6

Reactant 5

HCID 3283Diethyl EtherHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18418679HCID 18418679, compound

Product 1

HCID 54162779HCID 54162779, compoundYield 51%

Conditions

Temperature
0 °C

Procedure

(S2-[(Azepane-1-carbonyl)-amino]-3-methyl-butanoic acid (0.300 g, 1.23 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 (0.647 mL, 3.71 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.470 g, 1.24 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; solid 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (0.369 g, 1.24 mmol) was then added. After stirring for, sequentially, 15 minutes at 0° C. and 50 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 (60% EtOAc in hexane) to provide 0.31 g (51%) of the pure titled compound as a white foam: mp 32-50° C. APCI-MS m/z 486.3 (MH+).

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter stirring for, sequentially, 15 minutes at 0° C.
  3. custom50 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 (60% EtOAc in hexane)

Sources & evidence

ORD record
ord-ab42736521ae4088a669aa86ca56a777
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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