Sodium hydride → HCID 71007568, compound

HRID 1630491Notes

Reaction equation

HRID 1630491 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+].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]2[CH2:28][O:27]2)=[CH:22][CH:21]=1>CN(C=O)C.CO.C(Cl)Cl>[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]([CH2:28][CH:26]([C:23]3[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=3)[OH:27])[C:4]=2[CH2:3]1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 980482-(4-Methoxyphenyl)oxiraneHCID 7571332,3,4,9-Tetrahydro-2,6-dimethyl-1H-pyrido[3,4-b]indole

Product 1

HCID 71007568HCID 71007568, compoundYield 34.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

2,6-Dimethyl-2,3,4,9-tetrahydro-1H-β-carboline (1.0 g, 5.0 mmol) was dissolved in 15 mL DMF and sodium hydride (600 mg, 15 mmol) was added portionwise at 0° C. and stirred for 10 min. 2-(4-Methoxy-phenyl)-oxirane (900 mg, 6.0 mmol) was added dropwise at the 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 and filtered through a Celite bed. A cake of compound was formed which was dissolved in MeOH and DCM. This was again filtered through a Celite bed and the filtrate concentrated. The solid thus obtained was crystallized in ether & hexane to get 600 mg of 2-(2,6-dimethyl-1,2,3,4-tetrahydro-β-carbolin-9-yl)-1-(4-methoxy-phenyl)-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 7.27 (m, 3H), 7.24 (d, 1H), 7.00 (d, 1H), 6.98 (d, 2H), 4.98 (t, 1H), 4.09 (d, 2H), 3.81 (s, 3H), 3.67 (d, 1H), 3.32 (d, 1H), 2.79 (m, 3H), 2.7 (m, 1H), 2.49 (s, 3H), 2.45 (s, 3H). Separation by chiral HPLC provided enantiomers 20a and 20b. Optical rotations: Compound 20a, (−)10.20 (c 0.58, Chloroform, 99.61% HPLC purity); Compound 20b, (+)10.00 (c 0.59, Chloroform, 96.54% 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. filtrationfiltered through a Celite bed
  5. customA cake of compound was formed which
  6. filtrationThis was again filtered through a Celite bed
  7. concentrationthe filtrate concentrated
  8. customThe solid thus obtained
  9. customwas crystallized in ether

Sources & evidence

ORD record
ord-8e52d4ac10c444249ff643c98480bbdb
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

Loading…