Hydrochloric Acid → 2-(4-Bromo-3-formyl-phenoxy)-6-(2-methoxy-ethylamino)-nicotinonitrile

HRID 1483689Notes

Reaction equation

HRID 1483689 reaction equation
[Br:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][O:18][CH3:19])[CH:12]=[CH:11][C:8]=2[C:9]#[N:10])=[CH:4][C:3]=1[CH:22]1OCC[O:23]1.Cl>C1COCC1>[Br:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][O:18][CH3:19])[CH:12]=[CH:11][C:8]=2[C:9]#[N:10])=[CH:4][C:3]=1[CH:22]=[O:23]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 579690212-(4-Bromo-3-[1,3]dioxolan-2-yl-phenoxy)-6-(2-methoxy-ethylamino)-nicotinonitrile

Product 1

HCID 579691902-(4-Bromo-3-formyl-phenoxy)-6-(2-methoxy-ethylamino)-nicotinonitrileYield 87.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(4-bromo-3-[1,3]dioxolan-2-yl-phenoxy)-6-(2-methoxy-ethylamino)-nicotinonitrile (8) (1.0 g, 2.38 mmol) in THF (50 mL) was added HCl solution (1M/H2O, 20 mL). After overnight, the THF was evaporated under vacuum. The aqueous solution was extracted with EtOAc (2×50 mL). The organic layer was washed with water (3×50 mL), dried over MgSO4, filtered and evaporated in vacuo. Purification was accomplished by silica gel chromatography, eluting with 25%-100% EtOAc/hexanes gradient, to afford the desired product 780 mg (87% yield) as a white solid. 1H NMR (400 MHz, chloroform-d) δ ppm 10.34 (s, 1H), 7.80 (d, J=2.7 Hz, 1H), 7.67 (d, J=8.6 Hz, 1H), 7.60 (d, J=8.2 Hz, 1H), 7.30 (dd, J=8.8, 2.9 Hz, 1H), 6.13 (d, J=8.2 Hz, 1H), 5.24 (br. s., 1H), 3.42 (t, J=4.9 Hz, 2H), 3.35-3.27 (m, 5H).

Workup

  1. customthe THF was evaporated under vacuum
  2. extractionThe aqueous solution was extracted with EtOAc (2×50 mL)
  3. washThe organic layer was washed with water (3×50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customPurification
  8. washeluting with 25%-100% EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-0462afab5e6b407080062ff52425774a
Source dataset
uspto-grants-2016_08
Patent number
US09416146B2

Reaction notes

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