Thionyl Chloride → 3-Ethyl-pentanoic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide

HRID 905588

Reaction equation

HRID 905588 reaction equation
[CH2:1]([CH:3]([CH2:8][CH3:9])[CH2:4][C:5]([OH:7])=O)[CH3:2].S(Cl)(Cl)=O.[CH3:14][C:15]1[CH:20]=[C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH:18]=[C:17]([CH3:27])[C:16]=1[NH2:28].C(=O)(O)[O-].[Na+].[Cl-].[Na+].O.O>C(#N)C>[CH3:14][C:15]1[CH:20]=[C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH:18]=[C:17]([CH3:27])[C:16]=1[NH:28][C:5](=[O:7])[CH2:4][CH:3]([CH2:1][CH3:2])[CH2:8][CH3:9]

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 1344603-Ethylpentanoic acidHCID 230094142,6-Dimethyl-4-morpholin-4-yl-phenylamineHCID 131727349Sodium bicarbonate brine water

Product 1

HCID 116668733-Ethyl-pentanoic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amideYield 30.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
110 °C

Procedure

3-Ethylpentanoic acid (0.79 g) and thionyl chloride (0.44 mL) were mixed in acetonitrile (10 mL) and heated to 110° C. for 5 minutes in a sealed microwave process vial. 2,6-Dimethyl-4-morpholin-4-yl-phenylamine (1.25 g) dissolved in acetonitrile (10 mL) was added to the reaction mixture and heated to 150° C. for 15 minutes in a sealed microwave process vial. Saturated aqueous sodium bicarbonate/brine/water (1:1:1, 50 mL) was added to the crude mixture and it was extracted with ethyl acetate (3×50 mL). The combined organic phases were dried over magnesium sulfate and concentrated in vacuo. The crude product was recrystallized from hot toluene, and the product was collected by filtration, washed with cold toluene and dried in vacuo to furnish 0.59 g (30% yield) of the title compound as an off-white solid. LC-MS (m/z) 319 (MH+); tR=2.04, (UV, ELSD) 98%, 99%. 1H NMR (500 MHz, DMSO-d6): 0.87 (t, 6H), 1.35 (qui, 4H), 1.76 (m, 1H), 2.07 (s, 6H), 2.20 (d, 2H), 3.05 (t, 4H), 3.71 (t, 4H), 6.62 (s, 2H), 8.94 (s, 1H).

Workup

  1. additionwas added to the reaction mixture
  2. temperatureheated to 150° C. for 15 minutes in a sealed microwave process vial
  3. extractionwas extracted with ethyl acetate (3×50 mL)
  4. dry with materialThe combined organic phases were dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was recrystallized from hot toluene
  7. filtrationthe product was collected by filtration
  8. washwashed with cold toluene
  9. customdried in vacuo

Sources & evidence

ORD record
ord-69f458ec03ed48fb8e20abe8e0e4c27d
Source dataset
uspto-grants-2011_09
Patent number
US08012962B2

Linked notes

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