Hydrochloric Acid → 5-Hydroxy-2-(2-methoxyethoxy)isonicotinaldehyde

HRID 1847946Notes

Reaction equation

HRID 1847946 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:8]([O:11]COC)=[CH:9][N:10]=1)[CH:6]=[O:7].Cl.[C:16]([O-])([O-])=[O:17].[K+].[K+].C1[CH2:26][O:25][CH2:24]C1>O>[OH:11][C:8]1[C:5]([CH:6]=[O:7])=[CH:4][C:3]([O:2][CH2:1][CH2:24][O:25][CH3:26])=[N:10][CH:9]=1.[OH:11][C:8]1[CH:9]=[N:10][C:3]([O:2][CH2:1][CH2:24][O:25][CH3:26])=[C:4]([CH:5]=1)[CH:16]=[O:17]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 121807202-Methoxy-5-(methoxymethoxy)-4-pyridinecarboxaldehyde

Product 2

HCID 866907685-Hydroxy-2-(2-methoxyethoxy)isonicotinaldehydeYield 60%HCID 866907695-Hydroxy-2-(2-methoxyethoxy)nicotinaldehydeYield 11%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-methoxy-5-(methoxymethoxy)isonicotinaldehyde (1.27 g, 5.29 mol) in THF (5 mL) was added HCl (3 N, 4 mL). The reaction was stirred at 50° C. for 1 h, cooled to RT, and diluted with water (5 ml). The mixture was neutralized to pH 7-8 with solid K2CO3 and the aqueous layer was extracted with EtOAc (100 mL) twice. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes to give 5-hydroxy-2-(2-methoxyethoxy)isonicotinaldehyde (630 mg, 60%) and 5-hydroxy-2-(2-methoxyethoxy)nicotinaldehyde (120 mg, 11%). Data for 5-hydroxy-2-(2-methoxyethoxy)isonicotinaldehyde: 1H NMR (400 MHz, CDCl3) δ 9.98 (s, 1H), 9.50 (s, 1H), 8.07 (s, 1H), 7.02 (s, 1H), 4.51-4.39 (m, 2H), 3.81-3.72 (m, 2H), 3.47 (s, 3H). LRMS (M+H+) m/z 198.1. Data for and 5-hydroxy-2-(2-methoxyethoxy) nicotinaldehyde: 1H NMR (400 MHz, CDCl3) 10.3 (s, 1H), 7.99 (d, J=3.2 Hz, 1H), 7.58 (d, J=3.2 Hz, 1H), 7.18-7.07 (br, 1H), 4.54 (dd, J=5.4, 3.7 Hz, 2H), 3.84 (dd, J=5.4, 3.7 Hz, 2H), 3.49 (s, 3H); MS (ESI) m/z 198.1 [M+H]+.

Workup

  1. temperaturecooled to RT
  2. extractionthe aqueous layer was extracted with EtOAc (100 mL) twice
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated
  5. custompurified on silica gel using
  6. additiona mixture of EtOAc and hexanes

Sources & evidence

ORD record
ord-8e3de1bcf7824fecbd1e0d5ce8ec2fde
Source dataset
uspto-grants-2015_02
Patent number
US08952171B2

Reaction notes

Loading…