3-Benzyloxycyclobutanone

Diethyl ether (26.5 L) was added to the reactor (30-35 L reactor), and water cooling was applied on the reactor when additions started. The compound of the formula (VII) was added to the reactor (1.064 kg). Perchloric acid (0.932 L, 60percent) was pre-diluted with water (0.664 L) and added slowly to the reactor at 10°C, over 20-30 minutes. After the addition of acid was complete, cooling was stopped, and the reaction was left to stir (vigorously) overnight at ~20°C. The reaction was quenched by the addition of NaHC0A 2.4 eq portion of N-butyllithium (1.6 M in hexane, 243 mL) was added dropwise to a solution containing 2.4 eq of methyl methylsulfinyl methylsulfide (41 mL, 0.39 mmol) in 400 mL of tetrahydrofuran at -10 C. The reaction mixture was stirred at -10 C for 2 hours and then cooled to -78 C. The yellow reaction mixture was maintained at -78 C as a 1 eq portion of the ((1, 3-dibromopropan-2-yloxy)methyl)benzene (50 g, 0.16 mmol) in 85 mL of tetrahydrofuran was added dropwise. The reaction mixture was allowed to warm to room temperature overnight. The reaction mixture was added to brine and extracted twice with ethyl acetate. The combined organic layers were subject to the usual work up to provide 60 mL of dark red-brown liquid. This mixture of syn- and anti-dithioketal S-oxide intermediates was purified in three portions via silica gel column chromatography. Less polar impurities were eluted first with 3:7 ethyl acetate: hexane followed by elution of product with pure ethyl acetate. A total of 23.8 g of intermediate was obtained in this manner. The syn- and anti-dithioketal S-oxide intermediates (23.8 g, 0.09 mol) were dissolved in 600 mL of diethyl ether and treated with 34 mL of 35percent perchloric acid. After overnight stirring, the reaction mix was neutralized with sodium bicarbonate followed by purification via silica gel column chromatography (15:85 ethyl acetate: hexane) which provided the ketone (11.8 g, 41percent yield) as an orange-yellow liquid: A 2.4 eq portion of N-butyllithium (1.6 M in hexane, 243 mL) was added dropwise to a solution containing 2.4 eq of methyl methylsulfinyl methylsulfide (41 mL, 0.39 mmol) in 400 mL of tetrahydrofuran at -10 °C. The reaction mixture was stirred at -10 °C for 2 hours and then cooled to -78 °C. The yellow reaction mixture was maintained at -78 °C as a 1 eq portion of the ((1, 3- dibromopropan-2-yloxy)methyl)benzene (50 g, 0.16 mmol) in 85 mL of tetrahydrofuran was added dropwise. The reaction mixture was allowed to warm to room temperature overnight. The reaction mixture was added to brine and extracted twice with ethyl acetate. The combined organic layers were subject to the usual work up to provide 60 mL of dark red-brown liquid. This mixture of syn- and anti-dithioketal S-oxide intermediates was purified in three portions via silica gel column chromatography. Less polar impurities were eluted first with 3:7 ethyl acetate: hexane followed by elution of product with pure ethyl acetate. A total of 23.8 g of intermediate was obtained in this manner. The syn- and anti-dithioketal S-oxide intermediates (23.8 g, 0.09 mol) were dissolved in 600 mL of diethyl ether and treated with 34 mL of 35percent perchloric acid. After overnight stirring, the reaction mix was neutralized with sodium bicarbonate followed by purification via silica gel column chromatography (15:85 ethyl acetate: hexane) which provided the ketone 367 (11.8 g, 41percent yield) as an orange-yellow liquid: 1H NMR (400MHz, CDC1The preparation of the cyclobutanone 2 was based on the procedure reported by Ogura et al. (1984) Bull. Chem. Soc. Jpn. 57; 1637-42. A 2.4 eq portion of n-butyl lithium (1.6 M in hexane, 243 mL) was added dropwise to a solution containing 2.4 eq of methyl methylsulfinyl methylsulfide (41 mL, 0.39 mmoles) in 400 mL of tetrahydrofuran at -10° C. The reaction mix was then stirred at -10° C. for 2 hours and then cooled to -70° C. The yellow reaction mix was maintained at -70° C. and 1 equivalent of the dibromo species 1 (50 g, 0.16 mmoles) in 85 mL of tetrahydrofuran was added dropwise. The reaction mix was allowed to warm to room temperature overnight. The reaction mix was added to brine and extracted twice with ethyl acetate. The combined organic layers were subject to the usual work up to provide 60 mL of dark red-brown liquid. This mixture of syn- and anti-dithioketal S-oxide intermediates was purified in three portions via silica gel column chromatography (90 g silica). Less polar impurities were eluted first with 3:7 ethyl acetate:hexane followed by elution of product with pure ethyl acetate. A total of 23.8 grams of intermediate was obtained in this manner. In a second synthesis of 2 using identical conditions, 24.6 grams were obtained. The syn- and anti-dithioketal S-oxide intermediates (48.4 g, 0.18 moles) were dissolved in 1200 mL of diethyl ether and treated with 68 mL of 35percent perchloric acid. After overnight stirring, the reaction mix was neutralized with sodium bicarbonate followed by usual work up. Purification via silica gel column chromatography (15:85 ethyl acetate:hexane) provided the ketone 2 (23.6 g, 41percent from 1) as an orange-yellow liquid:

Molecular Weight:176.21
XLogP3:1.1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:176.083729621
Monoisotopic Mass:176.083729621
Topological Polar Surface Area:26.3
Heavy Atom Count:13
Complexity:175
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes