Benzyl Alcohol → Benzyl 6-(benzyloxy)pyridine-3-carboxylate

HRID 595178Notes

Reaction equation

[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:12]1[CH:27]=[CH:26][C:15]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])=[CH:14][N:13]=1>C1COCC1.[Cl-].[NH4+]>[CH2:3]([O:10][C:12]1[CH:27]=[CH:26][C:15]([C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])=[CH:14][N:13]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (1.2 g, 30.3 mmol, 60 wt %) was added to a solution of benzyl alcohol (3.28 g, 30.3 mmol) in THF (40 mL). The mixture was stirred at 0° C. under N2 for 1 hour. A solution of benzyl 6-chloronicotinate (5 g, 20.2 mmol) in THF (2 mL) was added to the mixture. The mixture was stirred at 20° C. for 12 hours. The mixture was diluted with saturated ammonium chloride solution and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford benzyl 6-(benzyloxy)nicotinate. MS ESI calc'd. for C20H18NO3 [M+H]+ 320. found 320. 1H NMR (400 MHz, DMSO-d6) δ 8.80 (d, J=2.4 Hz, 1H), 8.22-8.19 (m, 1H), 7.48-7.34 (m, 10H), 6.98 (d, J=8.4 Hz, 1H), 5.43 (s, 2H), 5.35 (s, 2H).

Workup

stirringThe mixture was stirred at 20° C. for 12 hours
extractionextracted with EtOAc
dry with materialThe organic layer was dried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by column chromatography on silica gel (petroleum ether/EtOAc)

Sources & evidence

ORD record: ord-a04af3143eb14c7fb1974919d45f0682
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242984B2

Reaction notes

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