Diethyl Ether → HCID 12017805, compound

HRID 990328Notes

Reaction equation

HRID 990328 reaction equation
[N:1]1([C:8]([NH:10][C@@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([OH:14])=O)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[C:28]1([CH:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:35][NH2:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(OCC)C>CN(C=O)C>[C:37]1([CH:34]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:35][NH:36][C:12]([C@@H:11]([NH:10][C:8]([N:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]2)=[O:9])[CH2:15][CH:16]([CH3:18])[CH3:17])=[O:14])[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 775752,2-DiphenylethylamineHCID 81531DiisopropylethylamineHCID 7530182(2S)-2-(azepane-1-carbonylamino)-4-methylpentanoic acid

Product 1

HCID 12017805HCID 12017805, compoundYield 85.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-[(Azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid (0.51 g, 2.0 mmol, Example 1, Step B) was dissolved in dry DMF (5 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (0.68 mL, 3.9 mmol) and solid O-benzotriazol-1-yl-N,N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.74 g, 2.0 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; 2,2-diphenylethylamine (0.38 g, 1.9 mmol, Aldrich, Milwaukee, Wis.) was then added. After additional 30 minutes stirring at 0° C., reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine, and was dried over Na2SO4. The solution was concentrated in vacuo, a white solid was obtained. Recrystallization from EtOAc-hexanes afforded 0.71 g (84%) of the pure titled compound as a white solid; mp 194-195° C. APCI-MS m/z 436.3 (MH+).

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter additional 30 minutes stirring at 0° C.
  3. customreaction mixture
  4. washthe resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution, brine
  5. dry with materialwas dried over Na2SO4
  6. concentrationThe solution was concentrated in vacuo
  7. customa white solid was obtained
  8. customRecrystallization from EtOAc-hexanes

Sources & evidence

ORD record
ord-6ad42629946943f6866e9447ccf0ea94
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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