Tetrabutylammonium Fluoride → N-(5-hydroxymethyl-pyridin-2-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamide

HRID 1430988Notes

Reaction equation

HRID 1430988 reaction equation
C([SiH2][O:6][C:7](C)(C)[C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15](=[O:34])[C:16]2[CH:21]=[C:20]([O:22][CH2:23][CH2:24][C:25]3[CH:29]=[CH:28][S:27][CH:26]=3)[CH:19]=[C:18]([O:30][CH:31]([CH3:33])[CH3:32])[CH:17]=2)=[N:12][CH:13]=1)(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[OH:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15](=[O:34])[C:16]2[CH:21]=[C:20]([O:22][CH2:23][CH2:24][C:25]3[CH:29]=[CH:28][S:27][CH:26]=3)[CH:19]=[C:18]([O:30][CH:31]([CH3:32])[CH3:33])[CH:17]=2)=[N:12][CH:13]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 178458726HCID 178458726, compound

Product 1

HCID 58528907N-(5-hydroxymethyl-pyridin-2-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamideYield 74.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

N-[5-(tert-Butyl-dimethyl-silanyloxymethyl)-pyridin-2-yl]-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamide (1.25 g, 2.37 mmol) was dissolved in THF (12 mL) and cooled to 0° C. Tetrabutylammonium fluoride (1.0 M solution in THF, 3.08 mL, 3.08 mmol) was added dropwise and the mixture was allowed to warm to rt over 24 hours. The reaction mixture was concentrated under reduced pressure and partitioned in EtOAc (30 mL) and water (30 mL). The organic layer was rinsed with water (20 mL), and then a saturated sodium chloride solution (20 mL), dried over sodium sulfate, filtered, and concentrated to yellow oil. After chromatography on silica gel with a gradient from 15-100% ethyl acetate-hexanes, N-(5-hydroxymethyl-pyridin-2-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamide (0.73 g, 74.9% yield) was obtained as a colorless oil. 1H NMR (300 MHz, DMSO-d6): δ 10.75 (s, 1H), 8.30 (s, 1H), 8.10 (d, J=6.0 Hz, 1H), 7.75 (d, J=6.0 Hz, 1H), 7.45 (d, J=3.0 Hz, 1H), 7.30 (s, 1H), 7.20 (s, 1H), 7.15 (s, 1H), 7.10 (d, J=3.0 Hz, 1H), 6.65 (s, 1H), 5.25 (t, 1H), 4.70 (m, 1H), 4.50 (d, J=3.0 Hz, 2H), 4.25 (t, 2H), 3.05 (t, 2H). 1.25 (s, 6H); LCMS (m/z): 413.1 [C22H24N2O4S+H]+.

Workup

  1. temperatureto warm to rt over 24 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. custompartitioned in EtOAc (30 mL)
  4. washThe organic layer was rinsed with water (20 mL)
  5. dry with materiala saturated sodium chloride solution (20 mL), dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to yellow oil

Sources & evidence

ORD record
ord-b984aabed44041cca7396ae23cd7996e
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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