Ammonium Chloride → tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

HRID 24001Notes

Reaction equation

HRID 24001 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH2:18][C:19](OCC)=[O:20])[N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Li+].[Cl-].[NH4+]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH2:18][CH2:19][OH:20])[N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 4148881Lithium borohydrideHCID 20792300tert-butyl 7-(2-ethoxy-2-oxoethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

Product 1

HCID 58230650tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

7-Ethoxycarbonylmethyl-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (synthetic methodology described in Published International Patent Appl. WO 00/33838) (6.11 g, 19.0 mmol) was dissolved in tetrahydrofuran (40 mL) at room temperature. The solution was place under argon. Lithium borohydride [2M in tetrahydrofuran] (22.8 mmol, 11.43 mL) was carefully added and the reaction was refluxed overnight (16 h). The mixture was poured into a solution of saturated ammonium chloride and extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered, and evaporated under vacuum to give a crude mixture, which was purified via column chromatography to give 7-(2-hydroxy-ethyl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (49% yield). 1H NMR (Cl3CD), δ 7.30 (d, 1H, J=7.6 Hz), 7.76 (d, 1H, J=7.6 Hz), 3.98 (m, 2H), 3.78 (m, 2H), 2.92 (m, 2H), 2.71 (m, 2H), 1.92 (m, 2H), 1.54 (s, 9H).

Workup

  1. temperaturethe reaction was refluxed overnight (16 h)
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated under vacuum
  6. customto give a crude mixture, which
  7. customwas purified via column chromatography

Sources & evidence

ORD record
ord-3cba0cc3ecac4ebda101fea45116709c
Source dataset
uspto-grants-2005_02
Patent number
US06855722B2

Reaction notes

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