3-Fluorobenzylic alcohol → 2-((3-fluorobenzyl)oxy)-7,8-dihydro-1,6-naphthyridin-5(6H)-one

HRID 533146Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].CC([O-])(C)C.[K+].Cl[C:17]1[CH:26]=[CH:25][C:24]2[C:23](=[O:27])[NH:22][CH2:21][CH2:20][C:19]=2[N:18]=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][O:6][C:17]1[CH:26]=[CH:25][C:24]2[C:23](=[O:27])[NH:22][CH2:21][CH2:20][C:19]=2[N:18]=1

Participants

Conditions

Temperature: 100 °C

Procedure

3-Fluorobenzyl alcohol (1.66 g, 13.14 mmol) was dissolved into DMF (25 mL) and treated with KOtBu (3.2 g, 26.29 mmol) and stirred for 30 min. The mixture was treated with 2-chloro-7,8-dihydro-1,6-naphthyridin-5(6H)-one and heated to 100° C. overnight. The mixture was adsorbed onto silica and purified (0 to 80% EtOAc/Hexanes) to give a semi-pure solid. This material was further purified on RP-HPLC (eluting with 40-90% MeCN/H2O with 0.1% TFA modifier) to give 840 mg of the compound, 2-((3-fluorobenzyl)oxy)-7,8-dihydro-1,6-naphthyridin-5(6H)-one. 1H NMR (400 MHz, CDCl3) δ 8.44 (1H, d, J=7.6), 7.38 (1H, dd, J=14.6, 7.6), 7.24 (1H, d, 7.5), 7.22 (1H, d, J=9.6), 7.04 (1H, t, J=8), 6.79 (1H, d, J=8.4), 5.79 (1H, br s), 5.45 (2H, s), 3.64 (2H, t, J=6.4), 3.10 (2H, t, J=6.4); LC-MS (M+H)=273.2.

Workup

custompurified (0 to 80% EtOAc/Hexanes)
customto give a semi-pure solid
customThis material was further purified on RP-HPLC (eluting with 40-90% MeCN/H2O with 0.1% TFA modifier)

Sources & evidence

ORD record: ord-bba2af565023458b944fdb16cb4f98cb
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853237B2

Reaction notes

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