ethyl 1-((9RS,10RS)-2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-piperidine carboxylate → 1-((9RS,10RS)-2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-piperidinemethanol

HRID 862728Notes

Reaction equation

HRID 862728 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:21]=[CH:20][C:19]2[CH:18]3[CH2:22][C:11]([C:23]([N:25]4[CH2:30][CH2:29][CH:28]([C:31](OCC)=[O:32])[CH2:27][CH2:26]4)=O)([C:12]4[C:17]3=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:10]=2[CH:9]=1>O1CCCC1>[Cl:7][C:8]1[CH:21]=[CH:20][C:19]2[CH:18]3[CH2:22][C:11]([CH2:23][N:25]4[CH2:26][CH2:27][CH:28]([CH2:31][OH:32])[CH2:29][CH2:30]4)([C:12]4[C:17]3=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:10]=2[CH:9]=1

Participants

4

Reactant 2

HCID 19698629ethyl 1-((9RS,10RS)-2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-piperidine carboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 196986711-((9RS,10RS)-2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-piperidinemethanolYield 99.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of lithium aluminum hydride (4.53 g, 119.5 mmol) in tetrahydrofuran (175 mL) was heated to reflux temperature and was treated dropwise with a solution of ethyl 1-((9RS,10RS)-2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-piperidine carboxylate (9.83 g, 23.9 mmol) in tetrahydrofuran (75 mL) at a rate sufficient to maintain reflux. Upon complete addition, the mixture was stirred for 1 h at reflux, then was cooled to 0° C. and quenched by sequential addition of water (4.5 mL), 10% aqueous sodium hydroxide (4.5 mL) and water (13.5 mL). The resulting milky suspension was treated with Celite, warmed to room temperature and stirred for 15 min. The solids were removed by filtration through Celite, the filter cake was washed with tetrahydrofuran/methanol (20:1, 2×200 mL), and the filtrate was evaporated. Trituration of the solid obtained with ethyl acetate/hexane (1:1, 50 mL) and evaporation of solvent afforded the title compound as a white solid (8.40 g, 23.7 mmol, 99%). 1H NMR (d6-DMSO): δ7.24 (m, 4H), 6.93 (m, 4H), 4.39 (brs, 1H, CH2OH), 4.30 (s, 1H, H--C(10)), 3.36-3.21 (m, 4H, CH2OH, CH2N), 2.96 (m, 2H, eq-H--C(2')), 2.46 (s, 2H, H--C(11)), 2.15 (m, 2H, ax-H--C(2')), 1.60 (m, 2H, eq-H--C(3')), 1.35 (m, 1H, H--C(4')), 1.10 (m, 2H, ax-H--C(3')).

Workup

  1. temperaturewas heated
  2. temperatureto reflux temperature
  3. temperatureto maintain
  4. temperaturereflux
  5. additionUpon complete addition
  6. temperatureat reflux
  7. customquenched by sequential addition of water (4.5 mL), 10% aqueous sodium hydroxide (4.5 mL) and water (13.5 mL)
  8. additionThe resulting milky suspension was treated with Celite
  9. temperaturewarmed to room temperature
  10. stirringstirred for 15 min
  11. customThe solids were removed by filtration through Celite
  12. washthe filter cake was washed with tetrahydrofuran/methanol (20:1, 2×200 mL)
  13. customthe filtrate was evaporated
  14. customTrituration of the solid obtained with ethyl acetate/hexane (1:1, 50 mL) and evaporation of solvent

Sources & evidence

ORD record
ord-5522ba6fa32d40a285e30a865dfe85aa
Source dataset
uspto-grants-1998_02
Patent number
US05719166

Reaction notes

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