Structure of 65862-01-3
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CAS No. : | 65862-01-3 |
Formula : | C7H10O2 |
M.W : | 126.15 |
SMILES Code : | O=C(C1(C2)CC2(C)C1)O |
MDL No. : | MFCD19228632 |
InChI Key : | TUFJVYRDYWRNOL-UHFFFAOYSA-N |
Pubchem ID : | 10441711 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P332+P313-P337+P313-P362-P403+P233-P405-P501 |
* 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 |
---|---|---|
66% | With diphenyl phosphoryl azide; triethylamine; at 30℃;Molecular sieve; | [0186] 5-2 (0.500 g, 3.96 mmol) was dissolved in tert-BuOH (19.8 mL). EtiN (0.802 g, 7.93 mmol, 1 .1 5 mL) and activated 3 A molecular sieves were added followed by diphenylphosphoryl azide (1.025 mL, 4.76 mmol). The resulting solution was stirred at 30 C for 4 h, and then heated to reflux overnight. The solution was cooled to rt and then concentrated under reduced pressure. The residual oil was diluted with EtOAc (20 mL) and H2O (20 mL), and extracted with EtOAc (4 x 20 mL). The combined organics were dried (NaiSCM) and concentrated to afford the crude product that was further purified by flash chromatography (81O2, Hexanes/EtOAc) to provide 5-3 (0.513 g, 66%) as a semi-pure white solid. ' 1NMR (400 MHz, CDCI.3) δ 4.87 (br s, N/7. 1 H), 1.85 (s, 6 H), 1.43 (s, 9 H), 1 .21 (s, 3 H); LC/MS (APCI) m/z 98.1 j ( 1 i i Ι ΝΧ '- ΠΟ1H I . |
35.7% | With diphenyl phosphoryl azide; triethylamine; at 20℃; for 28h;Reflux; | Diphenylphosphonic azide (0.340 mL, 1.577 mmol) was added dropwise to a solution of 3-methylbicyclo[l . l .l]pentane-l-carboxylic acid (0.199 g, 1.577 mmol) and TEA(0.220 mL, 1.577 mmol) in dry tert-butanol (6 mL). The solution was stirred at room temperature for 4 h and then heated to reflux for 24 h. The solvent was evaporated under reduced pressure and the residue was extracted three times with tert-butyl methyl ether. The combined organic phase was washed with saturated aqueous sodium bicarconate solution and dried over anhydrous magnesium sulfate. After filtration and evaporation of the solvent under reduced pressure the residue was purified by column chromatography (0-5% ethyl acetate in hexanes) to afford tert-butyl 3-methylbicyclo[l .l . l]pentan-l- ylcarbamate (0.111 g, 0.563 mmol, 35.7 % yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.74 (s, 6 H), 1.36 (s, 9 H), 1.17 (s, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | [ 0185] 5-1 (0.940 g, 4.52 mmol) was dissolved in anhydrous Et2() (15.1 mL) and cooled to -78 C. A solution of tert-butyllittrium (5.7M in pentane, 0.637 g, 9.94 mmol, 5.85 mL) was added dropwise, a d the solution was stirred at -78 C for 1 h. After 1 h, CCb was bubbled through the solution for 10 mins, and the reaction was allowed to warm to ri Diethyl ether (10 mL) was added, and the mixture was extracted with H2O (3 x 20 mL). The combined aqueous layers were acidified with 1M HQ, and then extracted with Et2.0 (3 x 20 mL). The combined organics were dried (MgS04) and concentrated under reduced pressure to afford 5-2 (0.501 g, 88%) as a white solid, which was carried forward without further purification.JH NMR (400 MHz, DMSO-de) δ 52.1 1 (br s, COO//. 1 H), 1 .82 (s, 6 }. 1.14 (s, 3 H). | |
50.9% | To a solution of l-iodo-3-methylbicyclo[l .l . l]pentane (1.62 g, 7.79 mmol; prepared according to Eur. J.Org. Chem. 1137-1155 (2000)) in diethyl ether (26 mL), a solution of tert-butyllithium- 184 -ATI-2514175vl (9.16 mL, 15.57 mmol, 1.7 M in pentane) was added over a period of 40 min at -78 C. After stirring the reaction mixture for 1 h at this temperature, carbon dioxide gas was bubbled through the reaction mixture for 5 min and then the mixture was allowed to warm to room temperature. The reaction mixture was extracted twice with a 5% aqueous sodium bicarbonate solution. The combined aqueous phases were acidified to pH 2- 3 with concentrated hydrochloric acid at 0 C, saturated with sodium chloride, and extracted with diethyl ether. The combined organic phases were dried and, after evaporation of the solvent under reduced pressure, purified by column chromatography (0-20% ethyl acetate in hexanes) to afford 3-methylbicyclo[l . l .l]pentane-l-carboxylic acid (0.5 g, 3.96 mmol, 50.9 % yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 12.21 (s, 1 H), 1.82 (s, 6 H), 1.14 (s, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; at 0 - 20℃; for 16h; | To a stirred solution of 3-methylbicyclo[l.l. l]pentane-l -carboxylic acid (3 g, 23.8 mmol) in DCM (100 mL) was added A, (9-dimethyl hydroxyl amine hydrochloride (3.48 g, 35.7 mmol) and Et3N (11.6 ml, 83.2 mmol) at rt. The mixture was then cooled to 0 C and T3P (50 wt.% in EtOAc, 6.43 g, 40.4 mmol) was added dropwise and reaction was warmed to rt. After 16 h, the reaction was quenched with water (100 mL) and extracted with DCM (3 x 100 mL). The combined organic layers were dried over Na SCL, filtered and concentrated. The residue was purified by chromatography (Si02, EtOAc/pet. ether) to provide Intermediate 10 as an oil (2.5 g, 62% yield). XH NMR (300 MHz, CDCl3) d 3.65 (s, 3H), 3.17 (s, 3H), 1.98 (s, 6 H), 1.18 (s, 3H). |
62% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; ethyl acetate; at 0 - 20℃; for 16h; | To a stirred solution of <strong>[65862-01-3]3-methylbicyclo[1.1.1]pentane-1-carboxylic acid</strong> (3 g, 23.8 mmol) in DCM (100 mL) was added N,O-dimethylhydroxylamine hydrochloride (3.48 g, 35.7 mmol) and Et3N (11.6 ml, 83.2 mmol) at rt. The mixture was then cooled to 0 C and T3P (50 wt.% in EtOAc, 6.43 g, 40.4 mmol) was added dropwise and reaction was warmed to rt. After 16 h, the reaction was quenched with water (100 mL) and extracted with DCM (3 x 100 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by chromatography (SiO2, EtOAc/pet. ether) to provide Intermediate 10 as an oil (2.5 g, 62% yield). 1H NMR (300 MHz, CDCl3) d 3.65 (s, 3H), 3.17 (s, 3H), 1.98 (s, 6 H), 1.18 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 20℃; for 2.16667h; | To a stirred solution of compound I-Al HC1 salt (100 mg, 0.34 mmol, HC1 salt) and I-A72 (0.06 mL, 0.41 mmol) in DCM (2 mL) were added HATU (193.56 mg, 0.51 mmol) and DIPEA (0.18 mL, 1.02 mmol) atRT for 10 min. The reaction mixture was stirred at RT for 2 h. The reaction mixture was diluted with DCM (3 mL) and washed with water (2 x 3 mL) The organic layer was dried over anhydrous magnesium sulphate, filtered and evaporated to give a residue. The residue was purified by prep HPLC to give 1-72 (30 mg, 0.08 mmol, 23% yield) as a solid. HPLC: Rt 8.810 min, 95.1%; Column: X-Select CSH C18 (4.6 X 150) mm, 3.5 pm; Mobile phase: A: 0.1% Formic acid in water: ACN (95:05), B: ACN; Flow Rate: 1.0 mL/min. LCMS : 367.15 (M+H), Rt 2.21 min, Column: X-select CSH C18 (3*50) mm, 2.5 pm. NMR (400 MHz, DMSO-d6) dH = 9.02 (d, 1H), 8.28-8.25 (m, 2H), 8.16-8.13 (m, 1H), 5.27-5.19 (m, 1H), 1.68-1.64 (m, 6H), 1.63-1.53 (m, 10H). Chiral method: Rt 10.68 min, 95.7%; column: DIACEL CHIRALPAK-IG (250x4.6mm, 5u), - Mobile Phase: A) n-Hexane+0.1%Iso-propyl-amine B) isopropyl alcohol (1:1), Isocratic:20%B; Wavelength: 271 nm, Flow: 1.0 mL/min. |
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