Thionyl Chloride → 1-(2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)piperidin-4-ol

HRID 1490181Notes

Reaction equation

HRID 1490181 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17](O)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.S(Cl)(Cl)=O.[OH:24][CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17]([N:28]4[CH2:29][CH2:30][CH:25]([OH:24])[CH2:26][CH2:27]4)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 79341Piperidin-4-olHCID 196986472-Chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid

Product 1

HCID 214806421-(2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)piperidin-4-olYield 82%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid (described in example 1j) (6.51 g, 24.1 mmol) in toluene (70 mL) was added thionyl chloride (2.28 mL, 31.3 mmol, 1.3 eq). The reaction was heated to reflux monitoring gas evolution with a mineral oil bubbler. The system reached a steady state within 40 min at which time it was slightly cooled and 4-hydroxypiperidine (6.08 g, 60.3 mmol, 2.5 eq) was added portionwise. A significant amount of heat is evolved and the reaction becomes dark. The suspension was heated to reflux for 2 h, cooled to room temperature and stirred for 18 h. The reaction was diluted with ethyl acetate (200 mL) and washed with 3 N HCl (2×100 mL), 2.5 N NaOH (2×100 mL) and saturated brine (200 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered, and reduced to an oil. The procedure yielded 6.95 g (82%) of the title compound as a viscous oil. No addition purification was required. 1H NMR (D6 -DMSO, 250 MHz) 7.63 (m, 1H), 7.21 (m, 6H), 4.41 (s, 1H), 4.18 (m, 1H), 3.65 (m, 2H), 3.25 (m, 2H), 2.76 (m, 2H), 1.90 (m, 2H), 1.38 (m, 2H) MS (CI, CH4) m/z 354 (M+1,100), 356 (36), 382 (M+29,19), 336 (27), 318 (9)

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux monitoring gas evolution with a mineral oil bubbler
  3. customwithin 40 min
  4. temperaturewas slightly cooled
  5. temperatureA significant amount of heat
  6. temperatureThe suspension was heated
  7. temperatureto reflux for 2 h
  8. washwashed with 3 N HCl (2×100 mL), 2.5 N NaOH (2×100 mL) and saturated brine (200 mL)
  9. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  10. filtrationfiltered

Sources & evidence

ORD record
ord-91333fee7e674328aaa07052056fc3f6
Source dataset
uspto-grants-1997_10
Patent number
US05681840

Reaction notes

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