Aluminium lithium hydride → HCID 68283904, compound

HRID 1630633Notes

Reaction equation

HRID 1630633 reaction equation
C[O:2][C:3](=O)[CH2:4][CH:5]([C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)[CH2:6][N:7]1[C:15]2[CH:14]=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=2[C:9]2[CH2:17][N:18]([CH3:21])[CH2:19][CH2:20][C:8]1=2.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:21][N:18]1[CH2:19][CH2:20][C:8]2[N:7]([CH2:6][CH:5]([C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)[CH2:4][CH2:3][OH:2])[C:15]3[CH:14]=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=3[C:9]=2[CH2:17]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 68283812HCID 68283812, compound

Product 1

HCID 68283904HCID 68283904, compoundYield 24.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-3-pyridin-4-yl-butyric acid methyl ester (300 mg, 0.795 mmol) in THF (5 mL) was added dropwise to a solution of LiAlH4 (93 mg, 2.37 mmol) in THF (10 mL). The reaction mixture was stirred at RT for 30 min. After consumption of starting material, the reaction mixture was cooled to −78° C. 0.2 mL of water and 0.2 mL of 15% NaOH solution was added and the reaction mixture was allowed to come to RT and diluted with THF and filtered. The filtrate was concentrated and the crude product was purified by passing through a column of silica gel (100-200 mesh) by using eluent 2% MeOH in DCM to obtain 69 mg of 4-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-3-pyridin-4-yl-butan-1-ol. 1H NMR (CDCl3, freebase) δ (ppm): 8.48 (d, 2H), 7.18 (s, 1H), 7.1 (d, 1H), 7.01 (d, 2H), 6.97 (d, 1H), 4.2 (dd, 1H), 4.15 (dd, 1H), 3.64 (d, 1H), 3.56 (m, 2H), 3.4 (m, 2H), 2.7 (m, 3H), 2.4 (m, 1H), 2.5 (s, 3H), 2.43 (s, 3H), 1.94 (m, 2H). Separation by chiral HPLC provided enantiomers II-224a-b.

Workup

  1. customAfter consumption of starting material
  2. temperaturethe reaction mixture was cooled to −78° C
  3. addition0.2 mL of water and 0.2 mL of 15% NaOH solution was added
  4. customto come to RT
  5. additiondiluted with THF
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customthe crude product was purified

Sources & evidence

ORD record
ord-33ce1cc2cbf9481086a5689bf22e65bc
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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