Chlorotrimethylsilane → HCID 21707576, compound

Temperature

-78 °C

A flame-dried 3-necked flask was charged with 2,4-difluoro-1-methoxymethylphenol (26, 0.84 g, 4.8 mmol) in 30 mL of freshly distilled THF under argon and this mixture was cooled to -78° C. (FIG. 2E). nBuLi (2.5 M solution in hexane, 2.2 mL, 5.43 mmol) was added to this reaction mixture which was allowed to stir at -78° C. for 2.5 hours under argon. Chlorotrimethyl silane (1.0 M solution in THF, 5.43 mL, 5.43 mmol) was then added to the deep pink colored mixture at -78° C. and then the acetone/dry ice bath was removed and the reaction was allowed to proceed at room temperature for 14 h. Sat. NH4Cl (~20 mL) was added to the mixture which was then stirred for an additional 10 minutes and then extracted with ethyl ether (3×10 mL). The combined organic solution was washed with brine, water and then dried (MgSO4) and filtered. The solvent was removed under vacuo to afford the crude product which was purified by flash chromatography on silica gel (EtOAc:hexanes; 5:95) to yield a yellow oil (0.8 g, 79%). 1H NMR (CDCl3) δ 7.09-7.17 (m, 1H, ArH), 6.68-6.74 (m, 1H, ArH), 5.13 (s, 2H, CH2), 3.52 (s, 3H, CH3), 0.36-0.37 (t, 9H, Si(CH3)3); FAB-MS 247 (MH+, 70), 229 (40), 219 (60), 189 (58), 157 (40), 133 (60), 79 (100).

1. customthe acetone/dry ice bath was removed
2. waitto proceed at room temperature for 14 h
3. additionSat. NH4Cl (~20 mL) was added to the mixture which
4. stirringwas then stirred for an additional 10 minutes
5. extractionextracted with ethyl ether (3×10 mL)
6. washThe combined organic solution was washed with brine, water
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customThe solvent was removed under vacuo
10. customto afford the crude product which
11. customwas purified by flash chromatography on silica gel (EtOAc:hexanes; 5:95)

ORD record

ord-4143ef063df54de487c7950c934c0166

Source dataset

uspto-grants-1999_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05973191