Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → (Racemic) 4-((tert-butyldiphenylsilyl)oxy)-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine

HRID 1777928Notes

Reaction equation

HRID 1777928 reaction equation
[Si:1]([O:18][CH:19]1[CH2:28][CH2:27][NH:26][C:25]2[N:24]=[C:23]([CH:29]=[O:30])[CH:22]=[CH:21][C:20]1=2)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=C[CH:43]=1.[C:48]([O-:51])(O)=O.[Na+]>CO>[Si:1]([O:18][CH:19]1[C:20]2[C:25](=[N:24][C:23]([CH:29]([O:51][CH3:48])[O:30][CH3:43])=[CH:22][CH:21]=2)[NH:26][CH2:27][CH2:28]1)([C:14]([CH3:17])([CH3:15])[CH3:16])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 516892Sodium BicarbonateHCID 1317347825-((Tert-butyldiphenylsilyl)oxy)-5,6,7,8-tetrahydro-1,8-naphthyridine-2-carbaldehyde2×

Product 1

HCID 131734781(Racemic) 4-((tert-butyldiphenylsilyl)oxy)-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 5-((tert-butyldiphenylsilyl)oxy)-5,6,7,8-tetrahydro-1,8-naphthyridine-2-carbaldehyde (intermediate 71, 300 mg, 0.720 mmol) in MeOH (10 ml) was treated with pyridinium p-toluenesulfonate (271 mg, 1.08 mmol) and heated to reflux for 16 h. The reaction mixture was allowed to cool to room temperature, treated with sat. aq. NaHCO3 and extracted with DCM (3×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 40:60) to give the title compound as a colorless oil. (UPLC-MS 3) tR 1.42; ESI-MS 463.5 [M+H]+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 16 h
  3. extractionextracted with DCM (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 40:60)

Sources & evidence

ORD record
ord-5cb6ce5493d14933bfc1db329f8beac2
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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