Sodium hydride → 2-(2,6-Dimethyl-1,2,3,4-tetrahydro-beta-carbolin-9-yl)-1-(4-fluoro-phenyl)-ethanol

HRID 1630489Notes

Reaction equation

HRID 1630489 reaction equation
[CH3:1][N:2]1[CH2:14][CH2:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:15])[CH:10]=3)[NH:5][C:4]=2[CH2:3]1.[H-].[Na+].[F:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]2[CH2:27][O:26]2)=[CH:21][CH:20]=1>CN(C=O)C>[CH3:1][N:2]1[CH2:14][CH2:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:15])[CH:10]=3)[N:5]([CH2:27][CH:25]([C:22]3[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=3)[OH:26])[C:4]=2[CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 7571332,3,4,9-Tetrahydro-2,6-dimethyl-1H-pyrido[3,4-b]indoleHCID 40652302-(4-Fluorophenyl)oxirane

Product 1

HCID 601969762-(2,6-Dimethyl-1,2,3,4-tetrahydro-beta-carbolin-9-yl)-1-(4-fluoro-phenyl)-ethanolYield 35.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,6-Dimethyl-2,3,4,9-tetrahydro-1H-β-carboline (500 mg, 2.5 mmol) was dissolved in 5 mL DMF and sodium hydride (250 mg, 6.24 mmol) was added portionwise at 0° C. and the mixture stirred for 10 min. 2-(4-Fluoro-phenyl)-oxirane (450 mg, 3.26 mmol) was added dropwise at same temperature and stirred for 12 h at RT. The reaction was monitored by TLC & LCMS. After consumption of starting material, the reaction mixture was quenched with ice cold water. The resultant solid was filtered and washed with water (100 mL) and hexane (100 mL), and the crude product was crystallized in EtOH:hexane (5:95 ratio) to obtain 300 mg of 2-(2,6-dimethyl-1,2,3,4-tetrahydro-β-carbolin-9-yl)-1-(4-fluoro-phenyl)-ethanol. 1H NMR (CDCl3, Free base) δ (ppm): 7.30 (m, 2H), 7.20 (d, 1H), 7.05 (m, 3H), 7.0 (d, 1H), 5.0 (t, 1H), 4.05 (d, 2H), 3.62 (d, 1H), 3.30 (d, 1H), 2.80 (m, 3H), 2.70 (m, 1H), 2.50 (s, 3H), 2.44 (s, 3H). Separation by chiral HPLC provided enantiomers 18a and 18b. Optical rotations: Compound 18a, (−)6.97 (c 0.56, Chloroform, 89.35% HPLC purity); Compound 18b, (+)13.03 (c 0.51, Chloroform, 99.51% HPLC purity).

Workup

  1. stirringstirred for 12 h at RT
  2. customAfter consumption of starting material
  3. customthe reaction mixture was quenched with ice cold water
  4. filtrationThe resultant solid was filtered
  5. washwashed with water (100 mL) and hexane (100 mL)
  6. customthe crude product was crystallized in EtOH:hexane (5:95 ratio)

Sources & evidence

ORD record
ord-9282727ee354440282a6e14f6821e4e2
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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