Triethylamine → 6-[3-(Tert-butyl-dimethyl-silanyloxy)-propoxy]-nicotinonitrile

HRID 2424979Notes

Reaction equation

HRID 2424979 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][N:15]=1.CCN(CC)CC>C(Cl)Cl.CN(C1C=CN=CC=1)C.[Cl-].[Na+].O>[C:4]([Si:1]([CH3:3])([CH3:2])[O:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][N:15]=1)([CH3:7])([CH3:6])[CH3:5]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 431521396-(3-Hydroxypropoxy)nicotinonitrile

Product 1

HCID 578454316-[3-(Tert-butyl-dimethyl-silanyloxy)-propoxy]-nicotinonitrileYield 69.5%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of t-butyldimethylsilyl chloride (0.93 g, 6.17 mmol) in CH2Cl2 (25 mL) was added 6-(3-hydroxypropoxy)nicotinonitrile (Example 66, 1 g, 5.61 mmol), Et3N (0.62 g, 6.17 mmol), and DMAP (0.014 g, 0.11 mmol). The mixture was stirred at rt for 18 h. The reaction mixture was diluted with brine and extracted with CH2Cl2 (3×25 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel flash chromatography (2:1 hexanes/EtOAc) to give the title compound (1.14 g, 69%). 1H NMR (400 MHz, CDCl3) δ 8.40 (dd, 1H), 7.69 (dd, 1H), 6.72 (dd, 1H), 4.40 (t, 2H), 3.73 (t, 2H), 1.90-1.98 (m, 2H), 0.82 (s, 9H), 0.02 (s, 6H).

Workup

  1. extractionextracted with CH2Cl2 (3×25 mL)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was purified by silica gel flash chromatography (2:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-4eeff0de683440c492d29ce8f6ecc9fd
Source dataset
uspto-grants-2011_06
Patent number
US07964622B2

Reaction notes

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