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Structure of 3-Hydroxycyclobutan-1-one
CAS No.: 15932-93-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 15932-93-1 |
Formula : | C4H6O2 |
M.W : | 86.09 |
SMILES Code : | O=C1CC(O)C1 |
MDL No. : | MFCD21604157 |
InChI Key : | VYZHGWJPDGIYDR-UHFFFAOYSA-N |
Pubchem ID : | 22486676 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H225 |
Precautionary Statements: | P210-P403+P235 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅲ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With dihydrogen peroxide; oxalic acid; lithium tetrakis(pentafluorophenyl)borate; In water; 1,2-dichloro-ethane; at 20.0℃; for 9.0h; | As shown in Tables 5 and 6, the Baeyer-Villiger oxidation reaction was investigated using various reactive substrates. As the catalyst, a borate salt of Li or Ca was used. In general, although the catalytic activity of a Ca borate salt was higher, since a Li borate salt was a commercially available product, and the amount thereof to be used was small due to its low molecular weight, the Li borate salt was first used (Examples 57, 58, 66 to 71, and 73). However, when the Li borate salt was not sufficient depending on the reactive substrate, and the chemical yield of the product was low, the Ca borate salt was used as the catalyst (Examples 59 to 65, 72, and 74 to 76). In Examples 66 to 72, when a cyclobutanone derivative was used as the reactive substrate, a corresponding lactone was obtained at a high yield in each case. Among the above Examples, in Examples 69 and 70, although an unstable reactive substrate, which had a halogen group at one carbon and a hydroxy group or a siloxy group at the carbon adjacent thereto and which was liable to form an epoxy ring, was used, no epoxidation occurred.Product of Example 67: colorless oil. TLC, Rf=0.1 (hexane-EtOAc=1:1); 1H NMR (CDCl3, 400 MHz) delta 2.54 (d, J=17.8, 1H), 2.58 (brs, 1H), 2.77 (dd, J=17.9, 5.6 Hz, 1H), 4.32 (d, J=10.1 Hz, 1H), 4.43 (dd, J=10.5, 4.6 Hz, 1H), 4.71 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43.6% | With sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; for 18.0h; | A mixture of N((5-(5-(difluoromethyl)- 1,3 ,4-oxadiazol-2-yl)pyridin-2-yl)methyl)-N-phenylpiperidine- 4-sulfonamide dihydrochioride (0.090 g, 0.172 mmol), <strong>[15932-93-1]3-hydroxycyclobutan-1-one</strong> (0.044 g, 0.517 mmol) and N,N-diisopropylethylamine (0.090 mL, 0.517 mmol) in dichloromethane (5 mL) was treated at the room temperature with sodium triacetoxyborohydride (0.073 g, 0.345 mmol), and stuffed at the same temperature for 18 hr. Then, saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous Mg504, filtered, and concentrated in vacuo. The residue was chromatographed (5i02, 12 g cartridge; methanol / dichloromethane = 0 % to 5 %) to give N((5-(5-(difluoromethyl)- 1,3 ,4-oxadiazol-2-yl)pyridin-2-yl)methyl)- 1 -(3-hydroxycyclob utyl)-N-phenylpiperidine-4-sulfonamide as pale orange solid (0.039 g, 43.6 %).?H NMR (400 MHz, DMSO-d6) oe 9.09 (d, 1 H, J = 2.2 Hz), 8.41 (dd, 1 H, J = 8.2,2.3 Hz), 7.72-7.68 (m, 1.25 H), 7.56 (s, 0.5 H), 7.49 (d, 2 H, J= 7.5 Hz), 7.43 (s, 0.25H), 7.38 - 7.31 (m, 2 H), 7.25 (t, 1 H, J= 7.3 Hz), 5.17 (s, 2 H), 4.93 (m, 1 H), 4.18 (m,0.5 H), 3.78 (m, 0.5 H), 3.00 - 2.80 (m, 2 H), 2.34 (m, 1 H), 2.15 - 2.03 (m, 4 H), 2.00(m, 1 H), 1.90 - 1.54 (m, 6 H); LRMS (ES) mlz 520.4 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.9% | With sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; for 18.0h; | A mixture of methyl4-((N-(3-chlorophenyl)piperidine-4- sulfonamido)methyl)benzoate hydrochloride (0.790 g, 1.720 mmol), <strong>[15932-93-1]3-hydroxycyclobutan-1-one</strong> (0.296 g, 3.439 mmol) and N,N-diisopropylethylamine (0.599 mL, 3.439 mmol) in dichloromethane (20 mL) was treated at the room temperature with sodium triacetoxyborohydride (0.729 g, 3.439 mmol), and stirred at the same temperature for 18 hr. Then, saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (Si02, 40 g cartridge; methanol / dichloromethane = 0 % to 5 %) to give methyl4-(((N-(3-chlorophenyl)- 1 -(3-hydroxycyclobutyl)piperidine)-4- sulfonamido)methyl)be nzoate as beige solid (0.830 g, 97.9 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.5% | With sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; for 18.0h; | A mixture of methyl6-((N-(3-chlorophenyl)piperidine-4- sulfonamido)methyl)nicotinate dihydrochloride (0.780 g, 1.570 mmol), <strong>[15932-93-1]3-hydroxycyclobutan-1-one</strong> (0.270 g, 3.140 mmol) and N,N-diisopropylethylamine (0.820 mL, 4.7 10 mmol) in dichloromethane (20 mL) was treated at the room temperature with sodium triacetoxyborohydride (0.665 g, 3.140 mmol), and stirred at the same temperature for 18 hr. Then, saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (Si02, 40 g cartridge; methanol / dichloromethane = 0 % to 5 %) to give methyl6-(((N-(3-chlorophenyl)- 1 -(3-hydroxycyclobutyl)piperidine)-4- sulfonamido)methyl)ni cotinate as beige solid (0.7 10 g, 91.5 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39.4% | With sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; for 18.0h; | A mixture of N(3-chlorophenyl)-N-(4-(5-(difluoromethyl)- 1,3 ,4-oxadiazol-2-yl)benzyl)piperidine-4- sulfonamide hydrochloride (0.050 g, 0.096 mmol), <strong>[15932-93-1]3-hydroxycyclobutan-1-one</strong> (0.025 g, 0.289 mmol) and N,N-diisopropylethylamine (0.034 mL, 0.193 mmol) in dichioromethane (5 mL) was treated at the room temperature with sodium triacetoxyborohydride (0.041 g, 0.193 mmol), and stirred at the same temperature for 18 hr. Then, saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (Si02, 12 g cartridge; methanol / dichloromethane = 0 % to 5 %) to give N(3-chlorophenyl)-N-(4-(5-(difluoromethyl)- 1,3 ,4-oxadiazol-2-yl)benzyl)- 1 -(3-hydroxy cyclobutyl)piperidine-4-sulfonamide as orange solid (0.021 g, 39.4 %).?H NMR (400 MHz, DMSO-d6) oe 8.04 - 7.95 (m, 2 H), 7.65 (s, 0.25 H), 7.56 - 7.42(m, 3.5 H), 7.41 -7.38 (m, 1.25 H), 7.37 -7.27 (m, 2 H), 5.11 (s, 2 H), 4.93 (m, 1 H),4.20 (m, 1 H), 3.03 - 2.88 (m, 2 H), 2.34 (m, 1 H), 2.16 - 2.05 (m, 4 H), 2.04 - 1.97 (m,2 H), 1.92 - 1.85 (m, 2 H), 1.79 - 1.58 (m, 3 H); LRMS (ES) mlz 553.2 (M÷+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32.3% | With sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; for 18.0h; | A mixture of N(4-(5-(difluoromethyl)- 1,3 ,4-oxadiazol-2-yl)benzyl)-N-(m-tolyl)piperidine-4-sulfonamide hydrochloride (0.090 g, 0.180 mmol), <strong>[15932-93-1]3-hydroxycyclobutan-1-one</strong> (0.047 g, 0.54 1 mmol) and N,N-diisopropylethylamine (0.063 mL, 0.36 1 mmol) in dichloromethane (5 mL) was treated at the room temperature with sodium triacetoxyborohydride (0.076 g, 0.361 mmol), and stirred at the same temperature for 18 hr. Then, saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed (Si02, 12 g cartridge; methanol / dichloromethane = 0 % to 5 %) to give N(4-(5-(difluoromethyl)- 1,3 ,4-oxadiazol-2-yl)benzyl)- 1 -(3-hydroxycyclobutyl)-N-(m-tol yl)piperidine-4-sulfonaniide as light yellow solid (0.031 g, 32.3 %).?H NMR (400 MHz, DMSO-d6) oe 7.98 (d, 2 H, J= 6.6 Hz), 7.66 (s, 0.25 H), 7.53 (s,0.5 H), 7.50 (d, 2 H, J= 8.3 Hz), 7.40 (s, 0.25 H), 7.27 -7.16 (m, 3 H), 7.04 (m, 1 H),5.05 (s, 2 H), 4.93 (m, 1 H), 4.14 (m, 0.5 H), 3.75 (m, 0.5 H), 3.19 (m, 1 H), 2.93 (m, 1H), 2.91 - 2.78 (m, 2 H), 2.33 (m, 1 H), 2.25 (s, 3 H), 2.13 - 2.02 (m, 3 H), 1.86 (m, 1H), 1.77 - 1.53 (m, 5 H); LRMS (ES) mlz 533.4 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With sodium cyanoborohydride; zinc(II) chloride; In methanol; at 20.0℃; for 4.0h; | General procedure: To a solution of 5-(tert-butyl)-N-(8-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)- 2,3,4,5-tetrahydro-1H-benzo[c]azepin-5-yl)-1,2,4-oxadiazole-3-carboxamide (180 mg, 0.36 mmol) and dihydrofuran-3(2H)-one (132 mg, 1.8 mmol) in MeOH (20 mL) were addedNaBH3CN (66 mg, 1.08 mmol) and ZnCl2(246 mg, 1.8 mmol). The mixture was stirred at rt for 16 h. After concentration and diluting with water (30 mL), the mixture was extracted with EtOAc (80 mL x 2). The combined organic layer was washed with H2O (60 mL) andconcentrated. The crude product was purified by prep-HPLC (CH3CN/H2O with 0.05%NH4Hco3as mobile phase) to give 5-(tert-butyl)-N-(8-(2-((1-methyl-1H-pyrazol-4- yl)amino)pyrimidin-4-yl)-2-(oxetan-3-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-5-yl)-1,2,4- oxadiazole-3-carboxamide as a yellow solid (114 mg, yield: 49%). ESI-MS (M+H)+: 544.3.1H NMR (400 MHz, CD3OD) delta: 8.30 (d, J = 5.2 Hz, 1H), 7.92-7.85 (m, 3H), 7.51 (s, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 5.2 Hz, 1H), 5.50 (d, J = 9.6 Hz, 1H), 4.67-4.55 (m, 4H), 3.84-3.70 (m, 3H), 3.80 (s, 3H), 2.95-2.89 (m, 1H), 2.76-2.72 (m, 1H), 2.15-2.12 (m, 1H), 1.95-1.92 (m, 1H), 1.40 (s, 9H). |