ChemicalBook CAS DataBase List 2-FLUORO-6-METHOXYPHENOL

2-FLUORO-6-METHOXYPHENOL synthesis

7synthesis methods

Product Name:2-FLUORO-6-METHOXYPHENOL
CAS Number:73943-41-6
Molecular formula:C7H7FO2
Molecular Weight:142.13

456-49-5 Synthesis

456-49-5
361 suppliers
$8.00/10g

73943-41-6
98 suppliers
$13.00/250mg

Yield: 80%

Reaction Conditions:

Stage #1:1-fluoro-3-methoxybenzene with n-butyllithium in tetrahydrofuran at -78 - -65; for 2 h;
Stage #2: with Trimethyl borate in tetrahydrofuran at -78; for 1.5 h;
Stage #3: with dihydrogen peroxide;acetic acid in tetrahydrofuran at 0;

Steps:

Following the procedure of Ladd and Weinstock,5 4.0 mL (9.4 mmol) of 2.36 M n-butyl lithium wasadded dropwise over 1 hr to a solution of 1.28 g (10 mmol) fluoroanisole (1) in 10.0 mL dry THF keptbelow -65 oC by a dry ice/acetone bath. The solution was stirred for 2 hrs at -78 oC under nitrogen. 1.17g (11 mmol) of trimethoxyborane in 2.00 mL dry THF was added dropwise over 1 hr at -78 oC and thesolution was stirred for an additional 30 mins at -78 °C. The solution was warmed to 0 oC and 0.88 mL(15 mmol) of glacial acetic acid was added followed by the dropwise addition of 1 mL (10 mmol) of 30%H2O2. The solution was stirred overnight at 25 °C. The solution was diluted with H2O (10 mL) andextracted with THF (2 X 10 mL). The combined ether extracts were washed with H2O (2 X 7 mL) and 10%Mohrs salt (2 X 3 mL). The ether phase was dried with MgSO4 and evaporated under reduced pressureto yield 1.16 g of (80%) 2-fluoro-6-methoxyphenol. Yields for successive repetitions: 174 mmol gave 15.5g (63%); 261 mmol gave 29.7 g (80%). 1H NMR (300 MHz, CDCl3) 6.82 - 6.63 (m, 1H), 5.51 (s, 1H), 3.90(s, 1H). 19F NMR (282 MHz, CDCl3) -137.61 ppm (m, 1F). EI-MS: m/z 142 (M+), 127.

References:

Maresh, Justin J.;Ralko, Arthur A.;Speltz, Tom E.;Burke, James L.;Murphy, Casey M.;Gaskell, Zachary;Girel, Joann K.;Terranova, Erin;Richtscheidt, Conrad;Krzeszowiec, Mark [Synlett,2014,vol. 25,# 20,art. no. ST-2014-S0514-1,p. 2891 - 2894] Location in patent:supporting information