Hydrochloric Acid → 3,3-Bis(((1,1-dimethylethyl)dimethylsilyl)oxymethyl)cyclobutanone-O-methyl oxime

3,3-Bis(hydroxymethyl)-1,1-dimethoxycyclobutane (1.35 g, 7.65 mmol) from Step A and 3.8 mL of 2M aqueous hydrochloric acid solution were added to 60 mL of THF and the reaction mixture was stirred at ambient temperature for 0.5 h, under a nitrogen atmosphere. The reaction mixture was neutralized by the addition of a strongly basic hydroxide resin then filtered and concentrated in vacuo. The residue was washed with THF and dissolved in 30 mL of anhydrous pyridine. To this solution was added 767 mg (9.2 mmol) of methoxylamine hydrochloride and the resultant solution was stirred for ~20 h at ambient temperature, under a nitrogen atmosphere. t-Butyldimethylsilyl chloride (3.5 g, 23 mmol) and 60 mL of anhydrous pyridine were then added and stirring continued overnight. The bulk of the solvent was evaporated in vacuo at 35°-40° C. and the concentrate dissolved in 200 mL of methylene chloride. The methylene chloride solution was washed with 100 mL of water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on a 1.5×50 cm silica gel column eluted @ 5 psi with 200 mL of hexane, followed by 200 mL of 2% acetone in hexane, followed by 200 mL of 3% acetone in hexane, followed by 200 mL of 4% acetone in hexane and finally 200 mL of 10% acetone in hexane, to give 583 mg (20% yield) of the title compound; MS DCI-NH3M/Z: 388 (M+H)+ ; 1H NMR (CDCl3) δ 0.04 (s, 12H), 0.87 (s, 18H), 2.61 (d, 4H), 3.58 (s, 4H), 3.82 (s, 3H).

1. filtrationthen filtered
2. concentrationconcentrated in vacuo
3. washThe residue was washed with THF
4. dissolutiondissolved in 30 mL of anhydrous pyridine
5. stirringstirring continued overnight
6. customThe bulk of the solvent was evaporated in vacuo at 35°-40° C.
7. dissolutionthe concentrate dissolved in 200 mL of methylene chloride
8. washThe methylene chloride solution was washed with 100 mL of water
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified on a 1.5×50 cm silica gel column
13. washeluted @ 5 psi with 200 mL of hexane

ORDレコード

ord-df3e718428eb4b82b1a1f65e66c2e7ef

出典データセット

uspto-grants-1993_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05246931