Diethyl Ether → HCID 54406267, compound

HRID 990342Notes

Reaction equation

HRID 990342 reaction equation
[CH3:1][CH:2]([CH3:23])[CH2:3][C@H:4]([NH:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:13][CH2:12]1)=[O:10])[C:5]([OH:7])=O.C(N(CC)C(C)C)(C)C.Cl.[F:34][C:35]1[CH:40]=[CH:39][C:38]([CH:41]([C:46]2[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=2)[CH2:42][CH2:43][CH2:44][NH2:45])=[CH:37][CH:36]=1.C(OCC)C>CN(C=O)C>[F:34][C:35]1[CH:40]=[CH:39][C:38]([CH:41]([C:46]2[CH:47]=[CH:48][C:49]([F:52])=[CH:50][CH:51]=2)[CH2:42][CH2:43][CH2:44][NH:45][C:5]([C@@H:4]([NH:8][C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)=[O:10])[CH2:3][CH:2]([CH3:1])[CH3:23])=[O:7])=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 664093HCID 664093, compoundHCID 18418679HCID 18418679, compound

Product 1

HCID 54406267HCID 54406267, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(S)-4-Methyl-2-[(4-phenyl-piperazine-1-carbonyl)-amino]pentanoic acid (0.300 g, 0.940 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 (0.490 mL, 2.81 mmol) and solid O-benzotriazol-1-yl-N,N,N,′,N′-tetramethyluronium hexafluorophosphate (0.356 g, 0.939 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; solid 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (0.280 g, 0.940 mmol) was then added. After stirring for, sequentially, 10 minutes at 0° C. and 35 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 a solid. Recrystallization from ether afforded 0.18 g (34%) of the pure titled compound as a white solid; mp 138-141° C. APCI-MS m/z 563.4 (MH+).

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter stirring for, sequentially, 10 minutes at 0° C.
  3. custom35 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 a solid
  8. customRecrystallization from ether

Sources & evidence

ORD record
ord-8bc82da2df014b9daaa9392d041f830d
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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