Hydrochloric Acid → HCID 67545385, compound

HRID 2176161Notes

Reaction equation

HRID 2176161 reaction equation
Cl.[F:2][C:3]([F:14])([F:13])[O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11]N)=[CH:7][CH:6]=1.[N:15]12[CH2:23][CH2:22][CH:19]([CH2:20][CH2:21]1)[C:18](=O)[CH2:17][CH2:16]2.Cl.O1CCOCC1>C(O)(=O)C>[F:2][C:3]([F:14])([F:13])[O:4][C:5]1[CH:10]=[CH:9][C:8]2[NH:11][C:18]3[CH:19]4[CH2:22][CH2:23][N:15]([CH2:16][C:17]=3[C:7]=2[CH:6]=1)[CH2:21][CH2:20]4

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 27773284-(Trifluoromethoxy)phenylhydrazine hydrochlorideHCID 64203071-Azabicyclo[3.2.2]nonan-4-one

Product 1

HCID 67545385HCID 67545385, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
150 °C

Procedure

In a 30 ml, microwave reaction tube were combined 4-(trifluoromethoxy)phenyl-hydrazine hydrochloride (1143 mg, 5.0 mmol; Alfa Aesar), 1-azabicyclo[3.2.2]nonan-4-one (696 mg, 5.0 mmol; Example 2A), 4 N HCl in dioxane (2.5 mL, 10.0 mmol; Aldrich), and acetic acid (15 mL). The reaction mixture was heated in a microwave to 150° C. (Biotage Personal Chemistry, maximum 300 W) for 15 minutes, then cooled to room temperature. The solvent was removed, and the residue was basified with 5 N sodium hydroxide and extracted with ethyl acetate (3×50 mL). The combined organic phases were concentrated in vacuo and purified by reverse-phase HPLC [Waters XBridge RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 20 minutes] to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 2.08 (td, J=7, 4 Hz, 4H), 2.99-3.13 (m, 3H), 3.23 (dd, J=14, 7 Hz, 2H), 4.21 (s, 2H), 6.92 (ddd, J=9, 2, 1 Hz, 1H), 7.16 (d, J=1 Hz, 1H), 7.28 (d, J=8 Hz, 1H); MS (DCI/NH3) m/z 297 (M+H)+.

Workup

  1. customIn a 30 ml, microwave reaction tube
  2. temperaturecooled to room temperature
  3. customThe solvent was removed
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. concentrationThe combined organic phases were concentrated in vacuo
  6. custompurified by reverse-phase HPLC [Waters XBridge RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 20 minutes]

Sources & evidence

ORD record
ord-72c0432b1d754f23bdbefd0d71fd171f
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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