Aluminium lithium hydride → (4-((2-(3-Chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)methanol

HRID 1508732Notes

Reaction equation

HRID 1508732 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]3[CH2:14][CH2:15][CH2:16][C:11]3=[C:10]([NH:17][C:18]3[CH:27]=[CH:26][C:21]([C:22](OC)=[O:23])=[CH:20][CH:19]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]3[CH2:14][CH2:15][CH2:16][C:11]3=[C:10]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([CH2:22][OH:23])=[CH:26][CH:27]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 90109954US11401286, Example 87

Product 1

HCID 90112337(4-((2-(3-Chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)methanolYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-((2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)benzoate (0.075 g, 0.19 mmol) in THF (5 mL) at 0° C. was added lithium aluminum hydride (1.0 M, 0.6 mL, 0.6 mmol). The mixture warmed to rt and stirred for 2 d. After this time, the reaction was quenched with water and NaOH (2 M), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound (0.049 g, 71%) as an off-white solid. MW=350.84. 1H NMR (DMSO-d6, 500 MHz) δ 8.15 (s, 1H), 7.91-7.89 (m, 1H), 7.76-7.73 (m, 1H), 7.45-7.40 (m, 2H), 7.32 (d, J=8.5 Hz, 2H), 7.23-7.19 (m, 3H), 5.11 (t, J=6.0 Hz, 1H), 4.48 (d, J=6.0 Hz, 2H), 2.91 (t, J=7.5 Hz, 2H), 2.83 (t, J=7.5 Hz, 2H), 2.08 (quin, J=7.5 Hz, 2H); APCI MS m/z 351 [M+H]+.

Workup

  1. customAfter this time, the reaction was quenched with water and NaOH (2 M)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by column chromatography (silica, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-78df5a394f6b4e2c9e8f5cecc862a63c
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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