Nicotinic Acid → 4-Formyl-2-methoxyphenyl pyridine-3-carboxylate

HRID 44447

Reaction equation

HRID 44447 reaction equation
[CH:1]1[CH:6]=[N:5][CH:4]=[C:3]([C:7]([OH:9])=[O:8])[CH:2]=1.[O:10]=[CH:11][C:12]1[CH:20]=[CH:19][C:17](O)=[C:14]([O:15][CH3:16])[CH:13]=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl.O>[CH:11]([C:12]1[CH:20]=[CH:19][C:17]([O:8][C:7](=[O:9])[C:3]2[CH:2]=[CH:1][CH:6]=[N:5][CH:4]=2)=[C:14]([O:15][CH3:16])[CH:13]=1)=[O:10]

Participants

7

Reactant 4

HCID 938Nicotinic AcidHCID 1183VanillinHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 8897804-Formyl-2-methoxyphenyl pyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of Niacin 1 (1.6 g, 13.1 mmol) in dichloromethane (10 mL) was added Vanillin 8 (2 g, 13.1 mmol), N-methyl morpholine (4.3 mL, 39 mmol) and EDCI.HCl (5 g, 26.2 mmol). The resulting mixture was stirred at ambient temp for 3 h. It was then diluted with water, extracted with dichloromethane, and the organic layer dried over anhydrous sodium sulfate and concentrated. The crude product thus obtained was then chromatographed using over a column of silica gel using petroleum ether:ethyl acetate (1:1) to afford the title compound as a off white solid (300 mg, 9%, mp (° C.): 92-94) 1H NMR (300 MHz, DMSO-D6): 10.02 (s, 1H), 9.25 (d, J=2 Hz, 1H), 8.93 (dd, J=5 & 1.5 Hz, 1H), 8.48 (dt, J=1.8 Hz & 8 Hz, 1H), 7.67 (m, 3H), 7.57 (d, J=8 Hz, 1H), 3.87 (s, 3H)); LCMS (m/z): 257.7 (M+1); HPLC: tRet: 6.486 (98.9%).

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialthe organic layer dried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product thus obtained
  5. customwas then chromatographed

Sources & evidence

ORD record
ord-27a5bf611e6f4369a2f8f23bcfff16de
Source dataset
uspto-grants-2013_09
Patent number
US08541435B2

Linked notes

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