Hydroquinone → HCID 50923074, compound

HRID 2176086Notes

Reaction equation

HRID 2176086 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[CH2:11][CH:12]3[NH:16][CH:15]([C:5]2=1)[CH2:14][CH2:13]3.C1(C=CC(O)=CC=1)O.[Na].[CH3:26][C:27]1[CH:32]=[CH:31][C:30]([CH:33]=[CH2:34])=[CH:29][N:28]=1>CS(C)=O.O>[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:34][CH2:33][C:30]1[CH:29]=[N:28][C:27]([CH3:26])=[CH:32][CH:31]=1)[C:6]1[CH2:11][CH:12]3[NH:16][CH:15]([C:5]2=1)[CH2:14][CH2:13]3

Participants

7

Reactant 4

HCID 785HydroquinoneHCID 88172-Methyl-5-vinylpyridineHCID 5360545SodiumHCID 67545269HCID 67545269, compound

Product 1

HCID 50923074HCID 50923074, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 2-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole (170 mg, 0.80 mmol; Example 4A), hydroquinone (9 mg, 0.08 mmol), and -32% sodium in paraffin (79 mg, 1.1 mmol; Aldrich) in anhydrous dimethyl sulfoxide (800 μL) was sealed in a septum-capped reaction tube. After thoroughly evacuating and purging the vessel with nitrogen, 2-methyl-5-vinylpyridine (143 mg, 1.2 mmol, International Publication No. WO2001/017968) was added, and the reaction was stirred at 100° C. for 48 hours. The thick mixture was cooled to room temperature, poured into water (5 mL), and extracted with ethyl acetate (3×). The combined organic phases were washed with water, filtered through diatomaceous earth, dried (Na2SO4), concentrated, and purified by chromatography on silica (0-5% gradient of concentrated aqueous ammonium hydroxide in acetonitrile). The resulting material was purified further 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)] to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 1.10-1.26 (m, 1H), 1.84-2.06 (m, 4H), 2.40 (s, 3H), 2.43 (s, 3H), 2.86 (dd, J=16, 4.6, 1H), 2.97 (ddd, J=14, 5.4, 5.4, 1H), 3.09 (ddd, J=14, 9.0, 6, 1H), 3.75-3.86 (m, 1H), 4.14 (ddd, J=15, 9.0, 5.4, 1H), 4.30 (ddd, J=15, 6, 5.4, 1H), 4.44 (d, J=4.6, 1H), 6.90 (d, J=8.3, 1H), 7.10 (d, J=7.9, 1H), 7.17 (d, J=8.3, 1H), 7.20-7.25 (m, 2H), 7.75 (d, J=2.1, 1H); MS (ESI) m/z 332 (M+H)+.

Workup

  1. customwas sealed in a septum-capped reaction tube
  2. customAfter thoroughly evacuating
  3. additionwas added
  4. temperatureThe thick mixture was cooled to room temperature
  5. extractionextracted with ethyl acetate (3×)
  6. washThe combined organic phases were washed with water
  7. filtrationfiltered through diatomaceous earth
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. custompurified by chromatography on silica (0-5% gradient of concentrated aqueous ammonium hydroxide in acetonitrile)
  11. customThe resulting material was purified further 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)]

Sources & evidence

ORD record
ord-80ed41462c9545099472f02f3a95c597
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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