Sodium hydride → 3-(3-Benzyloxy-propoxy)-5-chloro-2-hydroxy-benzaldehyde

HRID 2367997Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([OH:11])[C:5]([OH:10])=[C:6]([CH:9]=1)[CH:7]=[O:8].[H-].[Na+].[CH2:14]([O:21][CH2:22][CH2:23][CH2:24]Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CS(C)=O>[CH2:14]([O:21][CH2:22][CH2:23][CH2:24][O:11][C:4]1[C:5]([OH:10])=[C:6]([CH:9]=[C:2]([Cl:1])[CH:3]=1)[CH:7]=[O:8])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 5-chloro-2,3-dihydroxy-benzaldehyde (3.1 g, 17.7 mmol) in anhydrous DMSO (20 mL) was added NaH (60% in mineral oil, 1.50 g, 35.4 mmol) portion-wise and the mixture was stirred for 30 minutes. The solution was cooled to 0° C. and a solution of 3-benzyloxy-1-bromopropane (3.1 mL, 17.7 mmol) in DMSO (3 mL) was added dropwise over 10 minutes period. The ice bath was removed. After overnight, the solution was diluted with EtOAc (100 mL), washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The product was purified by silica gel column chromatography (2:1 hexanes-EtOAc mobile phase) generating the title compound (5.3 g, 16.6 mmol, 94%) as a light yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.81 (s, 1H), 9.87 (s, 1H), 7.42-7.28 (m, 5H), 7.17 (s, 1H), 7.08 (s, 1H), 4.53 (s, 2H), 4.17 (t, J=6.2 Hz, 2H), 3.69 (t, J=5.8 Hz, 2H), 2.15 (t, J=6.2 Hz, 2H).

Workup

customThe ice bath was removed
waitAfter overnight
additionthe solution was diluted with EtOAc (100 mL)
washwashed with water, brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe product was purified by silica gel column chromatography (2:1 hexanes-EtOAc mobile phase)

Sources & evidence

ORD record: ord-34fb0cb475be467596a76b3626ffdabd
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08703742B2

Reaction notes

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