Hydroquinone → HCID 59285341, compound

HRID 2176111Notes

Reaction equation

HRID 2176111 reaction equation
[Na].[CH3:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]1[CH2:12][CH:13]3[N:18]([CH3:19])[CH:17]([C:6]2=1)[CH2:16][CH2:15][CH2:14]3.[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]=[CH2:28])=[CH:23][N:22]=1.C1(C=CC(O)=CC=1)O>CS(C)=O.O>[CH3:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:28][CH2:27][C:24]1[CH:23]=[N:22][C:21]([CH3:20])=[CH:26][CH:25]=1)[C:7]1[CH2:12][CH:13]3[N:18]([CH3:19])[CH:17]([C:6]2=1)[CH2:16][CH2:15][CH2:14]3

Participants

7

Reactant 4

HCID 785HydroquinoneHCID 88172-Methyl-5-vinylpyridineHCID 5360545SodiumHCID 67544025HCID 67544025, compound

Product 1

HCID 59285341HCID 59285341, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A reaction flask with a septum cap was charged with 30% sodium metal dispersion in paraffin wax (0.30 g, 4.0 mmol; Aldrich) and a solution of 2,12-dimethyl-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole (0.48 g, 2.0 mmol; Example 114A) in dimethyl sulfoxide (4 mL). The vessel was sealed, flushed with nitrogen, and stirred for 10 minutes. A solution of 2-methyl-5-vinylpyridine (0.238 g, 2.0 mmol; prepared as described in International Publication No. WO 2001017968) and hydroquinone (0.072 g, 0.66 mmol; Aldrich) in anhydrous dimethyl sulfoxide (1.5 mL) was added and the reaction was heated at 100° C. for 72 hours. After cooling the mixture to room temperature, it was poured into water and extracted with ethyl acetate (4×25 mL). The combined organic extracts were washed with brine, concentrated, and purified by reverse-phase HPLC [Waters XBridge™ C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 15 minutes] to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 0.82-1.00 (m, 1H), 1.17-1.30 (m, 1H), 1.32-1.42 (m, 1H), 1.55-1.64 (m, 1H), 1.78-1.99 (m, 3H), 2.15 (s, 3H), 2.40 (s, 6H), 2.66 (dd, J=17, 7 Hz, 1H), 3.06-3.15 (m, 3H), 4.03 (t, J=3 Hz, 1H), 4.30-4.37 (m, 2H), 6.95 (dd, J=8, 1 Hz, 1H), 7.08-7.14 (m, 2H), 7.26 (d, J=8 Hz, 1H), 7.32 (dd, J=8, 2 Hz, 1H), 7.82 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 360 (M+H)+.

Workup

  1. customA reaction flask with a septum cap
  2. customThe vessel was sealed
  3. customflushed with nitrogen
  4. temperatureAfter cooling the mixture to room temperature
  5. extractionextracted with ethyl acetate (4×25 mL)
  6. washThe combined organic extracts were washed with brine
  7. concentrationconcentrated
  8. custompurified by reverse-phase HPLC [Waters XBridge™ C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 15 minutes]

Sources & evidence

ORD record
ord-e2c188cbf3034d5990361db2906ceac6
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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