Tetrahydrofuran → 1-Fluoro-4-(1-methoxy-2-methylpropan-2-yl)benzene

Sodium hydride (1.664 g, 41.6 mmol, 60% dispersion in mineral oil) was suspended in dry THF (18 ml) under N2 and 2-(4-fluorophenyl)-2-methylpropan-1-ol (3.500 g, 20.8 mmol) in dry THF (18 ml) was slowly added to the suspension at 0° C. After complete addition the reaction was warmed to r.t. and left for 1 h. Iodomethane (6.5 ml, 0.104 mmol) was slowly added at r.t. and the reaction left for 3 h. The reaction was quenched by slow addition of H2O (35 ml). The layers were separated and the aqueous layer was extracted with EtOAc (3×35 ml). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give the crude product. The product was purified by silica flash column chromatography using between 100% heptane to 10% EtOAc:90% heptane as eluent to give the product as a colourless oil (2.991 g, 79%): LC purity 98% (ret. time, 2.16 min); 1H NMR (500 MHz, CDCl3) δH 7.40-7.32 (m, 2H), 7.11-6.96 (m, 2H), 3.39 (s, 2H), 3.33 (s, 3H), 1.33 (s, 6H).

1. additionAfter complete addition the reaction
2. waitthe reaction left for 3 h
3. customThe reaction was quenched by slow addition of H2O (35 ml)
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with EtOAc (3×35 ml)
6. dry with materialThe combined organic layers were dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give the crude product
10. customThe product was purified by silica flash column chromatography

ORD record

ord-2cb8712b9b874009be764cf25dcdd06b

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580762B2