Water → 1-(9,10-Dihydro-9,10-methanoanthracen-9-ylmethyl)4-piperidinemethanol

HRID 862731Notes

Reaction equation

HRID 862731 reaction equation
[CH:1]1[C:14]2[C:13]3([C:16]([N:18]4[CH2:23][CH2:22][CH:21]([C:24](OCC)=[O:25])[CH2:20][CH2:19]4)=O)[CH2:15][CH:6]([C:7]4[C:12]3=[CH:11][CH:10]=[CH:9][CH:8]=4)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].O>O1CCCC1>[CH:11]1[C:12]2[C:13]3([CH2:16][N:18]4[CH2:23][CH2:22][CH:21]([CH2:24][OH:25])[CH2:20][CH2:19]4)[CH2:15][CH:6]([C:5]4[C:14]3=[CH:1][CH:2]=[CH:3][CH:4]=4)[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium Hydroxide2×HCID 19698661HCID 19698661, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 196986601-(9,10-Dihydro-9,10-methanoanthracen-9-ylmethyl)4-piperidinemethanolYield 87.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 1-(9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-piperidine carboxylate (33.0 g, 88.4 mmol) in tetrahydrofuran (50 mL) was added dropwise to a suspension of lithium aluminum hydride (4.70 g, 123.8 mmol) in tetrahydrofuran (70 mL) held at reflux temperature. Upon complete addition, the mixture was held at reflux for 2 h, then was cooled to 0° C. and treated sequentially with 10% aqueous sodium hydroxide (4.7 mL), water (4.7 mL) and 10% aqueous sodium hydroxide (14.1 mL). The resulting white slurry was stirred for 30 minutes, treated with diatomaceous earth (25 g) and filtered through a pad of diatomaceous earth. The filter cake was washed with tetrahydrofuran/methanol (20:1, 2×200 mL). The filtrate was evaporated to give the title compound as a tan solid (23.5 g, 77.0 mmol, 87%) 1H NMR (d6-DMSO): δ7.25 (m, 2H), 7.18 (m, 2H), 4.38 (t, J=5.2 Hz, 1H, CH2OH), 4.29 (s, 1H, H--C(10)), 3.32 (s, 2H, CH2N), 3.21 (m, 2H, CH2OH), 2.97 (d, J=11.2 Hz, 2H, eq-H--C(2')), 2.44 (s, 2H, H--C(11)), 2.14 (dd, J=11.2, 11.2 Hz, ax-H--C(2')), 1.58 (d, J=11.0 Hz, eq-H--C(3')), 1.34 (m, 1H, H--C(4')), 1.10 (ddd, J=3.5, 11.0, 11.2 Hz, 2H, ax-H--C(3')).

Workup

  1. temperatureat reflux temperature
  2. additionUpon complete addition
  3. temperatureat reflux for 2 h
  4. additiontreated with diatomaceous earth (25 g)
  5. filtrationfiltered through a pad of diatomaceous earth
  6. washThe filter cake was washed with tetrahydrofuran/methanol (20:1, 2×200 mL)
  7. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-19ab48a1097441feb8acb80df59d2efc
Source dataset
uspto-grants-1998_02
Patent number
US05719166

Reaction notes

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