Sodium hydride → HCID 68283912, compound

HRID 1469525Notes

Reaction equation

HRID 1469525 reaction equation
[C:1]([C:5]1[CH:13]=[CH:12][C:11]2[NH:10][C:9]3[CH2:14][CH2:15][N:16]([CH3:18])[CH2:17][C:8]=3[C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[O:21]1[CH2:23][CH:22]1[C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1>CN(C=O)C>[C:1]([C:5]1[CH:13]=[CH:12][C:11]2[N:10]([CH2:23][CH:22]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)[OH:21])[C:9]3[CH2:14][CH2:15][N:16]([CH3:18])[CH2:17][C:8]=3[C:7]=2[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 67311353HCID 67311353, compound

Product 1

HCID 68283912HCID 68283912, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 8-tert-butyl-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.0 g, 4.1 mmol) in DMF (6 mL) was added sodium hydride (495 mg, 12.3 mmol) under nitrogen at 0° C. and stirred for 10 min. A solution of 4-(oxiran-2-yl)pyridine (898 mg, 7.4 mmol) in DMF (2 mL) was added dropwise into the reaction mixture at RT and stirred for 12 h. The progress of reaction was monitored by TLC and LCMS. The reaction mass was poured in ice-cold water and extracted with EtOAc (2×100 mL). The combined organic layer was washed with water (5×50 mL), dried over anhydrous sodium sulfate and concentrated. The residue was re-crystallized with hexane to yield 2-(8-tert-butyl-2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.7 (d, 2H), 7.3 (s, 1H), 7.2 (d, 1H), 7.19 (d, 2H), 7.17 (d, 1H), 4.7 (t, 1H), 4.0 (d, 2H), 3.5 (dd, 2H), 2.82 (m, 1H), 2.7 (m, 2H), 2.58 (m, 1H), 2.4 (s, 3H), 1.4 (s, 9H). Separation by chiral HPLC provides enantiomers II-68a-b.

Workup

  1. stirringstirred for 12 h
  2. customThe progress of reaction
  3. additionThe reaction mass was poured in ice-cold water
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe combined organic layer was washed with water (5×50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was re-crystallized with hexane

Sources & evidence

ORD record
ord-1654e894a7f1438e95f3c7d3d51ed5ac
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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