Aluminium lithium hydride → HCID 68283787, compound

HRID 1630579Notes

Reaction equation

HRID 1630579 reaction equation
C[O:2][C:3]([C:5]1[CH:13]=[CH:12][C:11]2[N:10]([CH2:14][CH:15]([OH:22])[C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[C:9]3[CH2:23][CH2:24][N:25]([CH3:27])[CH2:26][C:8]=3[C:7]=2[CH:6]=1)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:2][CH2:3][C:5]1[CH:13]=[CH:12][C:11]2[N:10]([CH2:14][CH:15]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[OH:22])[C:9]3[CH2:23][CH2:24][N:25]([CH3:27])[CH2:26][C:8]=3[C:7]=2[CH:6]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 68283316HCID 68283316, compound

Product 1

HCID 68283787HCID 68283787, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(2-hydroxy-2-pyridin-4-yl-ethyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylic acid methyl ester (180 mg, 0.493 mmol) in dry THF (12 mL) was portionwise added LAH (56 mg, 1.479 mmol) under nitrogen atmosphere, and the reaction mixture stirred at RT for 2 h. The reaction mixture was cooled to −78° C. and quenched with ice water (0.6 mL), 10% NaOH (0.6 mL) and water (1.8 mL), and the solid filtered. The filtrate was concentrated and the residue was purified by reverse phase HPLC to yield 2-(8-hydroxymethyl-2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol. 1H NMR (CD3OD, freebase) δ (ppm): 8.4 (d, 2H), 7.4 (s, 1H), 7.27-7.38 (m, 3H), 7.18 (d, 1H), 5.1 (t, 1H), 4.62 (s, 2H), 4.3 (d, 2H), 4.0 (dd, 2H), 3.2 (m, 1H), 3.1 (m, 2H), 2.73 (m, 1H), 2.7 (s, 3H). Separation by chiral HPLC provides enantiomers II-60a-b.

Workup

  1. temperatureThe reaction mixture was cooled to −78° C.
  2. customquenched with ice water (0.6 mL), 10% NaOH (0.6 mL) and water (1.8 mL)
  3. filtrationthe solid filtered
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-3fd963ad11a04cf8be131be817d9d141
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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