Sodium hydride → (S)-1-(2,3-bis((tert-butyldimethylsilyl)oxy)propyl)-5-methyl-1H-indole-2-carbonitrile

HRID 1505664Notes

Reaction equation

HRID 1505664 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]#[N:12])=[CH:5]2.[H-].[Na+].Cl[CH2:16][C@@H:17]([CH2:26][O:27][Si:28]([CH3:34])([CH3:33])[C:29]([CH3:32])([CH3:31])[CH3:30])[O:18][Si:19]([CH3:25])([CH3:24])[C:20]([CH3:23])([CH3:22])[CH3:21]>CN(C=O)C.O>[Si:19]([O:18][C@H:17]([CH2:26][O:27][Si:28]([C:29]([CH3:30])([CH3:32])[CH3:31])([CH3:33])[CH3:34])[CH2:16][N:7]1[C:8]2[C:4](=[CH:3][C:2]([CH3:1])=[CH:10][CH:9]=2)[CH:5]=[C:6]1[C:11]#[N:12])([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 199947895-methyl-1H-indole-2-carbonitrileHCID 90405653(R)-5-(chloromethyl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane

Product 1

HCID 90405548(S)-1-(2,3-bis((tert-butyldimethylsilyl)oxy)propyl)-5-methyl-1H-indole-2-carbonitrileYield 48.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 39 mg of 5-methyl-1H-indole-2-carbonitrile (0.25 mmol) in 0.5 mL of DMF 15 mg of NaH (60% in oil, 0.375 mmol) was added and mixture was stirred for 30 min. Then 170 mg of (R)-5-(chloromethyl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane (0.5 mmol) was added and stirring continued for 24 hs. The reaction mixture was diluted with 10 mL of water and extracted with DCM. Combined organic extracts dried over sodium sulfate, concentrated and purified using silica gel column eluting with hexane-ethyl acetate 50:1 to afford 56 mg of (S)-1-(2,3-bis((tert-butyldimethylsilyl)oxy)propyl)-5-methyl-1H-indole-2-carbonitrile. 1H NMR (600 MHz, CDCl3): δ 8.09 (d, 1H, J=8.8 Hz), 7.35 (s, 1H), 7.24 (d, 1H, J=8.8 Hz), 7.18 (s, 1H), 4.04 (m, 1H), 3.82 (m, 1H), 3.77 (m, 2H), 3.68 (m, 1H), 2.43 (s, 3H), 1.08 (m, 18H), 0.26 (m, 12H).

Workup

  1. stirringstirring
  2. extractionextracted with DCM
  3. dry with materialCombined organic extracts dried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified
  6. washeluting with hexane-ethyl acetate 50:1

Sources & evidence

ORD record
ord-60fcfde04cc742eea7d744f2aae105c8
Source dataset
uspto-grants-2015_12
Patent number
US09216993B2

Reaction notes

Loading…