Diisopropylethylamine → Ethyl 2-[(benzyloxy)amino]nicotinate

HRID 601137Notes

Reaction equation

HRID 601137 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[N:7][C:6]=1Cl)[CH3:2].Cl.[CH2:14]([O:21][NH2:22])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)C(C)C)(C)C>O1CCOCC1>[CH2:14]([O:21][NH:22][C:6]1[N:7]=[CH:8][CH:9]=[CH:10][C:5]=1[C:4]([O:3][CH2:1][CH3:2])=[O:12])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 102312Benzyloxyamine hydrochlorideHCID 2796614Ethyl chloronicotinate

Product 1

HCID 59224790Ethyl 2-[(benzyloxy)amino]nicotinateYield 53%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2-Chloro-nicotinic acid ethyl ester (4.55 g, 24.6 mmol), O-benzylhydroxyamine hydrochloride (7.85 g, 49.2 mmol) and N,N-diisopropylethylamine (6.36 g, 49.2 mmol) in 10 mL 1,4-dioxane were reacted in a sealed tube at 120° C. for 48 hours. The reaction mixture was partitioned between ethyl acetate and 5% aqueous sodium bicarbonate. The aqueous layer was re-extracted with ethyl acetate (2×50 mL). The organic layers were combined and dried over sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel eluting with hexane and ethyl acetate (9:1) to provide the title compound (3.5 g, 53%). MS (DCI) m/z 273 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and 5% aqueous sodium bicarbonate
  2. extractionThe aqueous layer was re-extracted with ethyl acetate (2×50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel eluting with hexane and ethyl acetate (9:1)

Sources & evidence

ORD record
ord-76eaeee7be724f1aa7b40be7706fbafa
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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