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CAS No. : | 2987-06-6 | MDL No. : | MFCD10697867 |
Formula : | C13H16O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | FFGVIYUANJAFJS-UHFFFAOYSA-N |
M.W : | 204.27 | Pubchem ID : | 10987369 |
Synonyms : |
|
Num. heavy atoms : | 15 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.46 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 59.42 |
TPSA : | 26.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.26 cm/s |
Log Po/w (iLOGP) : | 2.32 |
Log Po/w (XLOGP3) : | 1.81 |
Log Po/w (WLOGP) : | 2.56 |
Log Po/w (MLOGP) : | 1.93 |
Log Po/w (SILICOS-IT) : | 3.19 |
Consensus Log Po/w : | 2.36 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.34 |
Solubility : | 0.924 mg/ml ; 0.00452 mol/l |
Class : | Soluble |
Log S (Ali) : | -1.98 |
Solubility : | 2.13 mg/ml ; 0.0104 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -3.87 |
Solubility : | 0.0274 mg/ml ; 0.000134 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.92 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
95.2% | With hydrogenchloride In tetrahydrofuran; water at 20℃; | To a solution of 1-ethylene acetal-4-benzyloxy-cyclohexane (17) (3.13 g, 12.6 mmol) in 50 ml THF, aqueous hydrochloric acid (1N, 30 ml) was added at rt. The reaction was stirred overnight and neutralized with sodium bicarbonate (sat.). The product was extracted with ethyl acetate and the organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by the silica gel chromatography (20percent ethyl acetate in hexane) yielded 2.45 g (95.2percent) of the title ketone. 1H NMR (CDCl3) δ: 1.95-2.62 (8H, m, 4.x.-CH2-), 3.82 (1H, m, -CH-), 4.59 (2H, s, Ph-CH2-), 7.28-7.36 (5H, m, Ph-H). |
19.2 g | With hydrogenchloride In tetrahydrofuran; water at 20℃; for 18 h; Inert atmosphere | [532] Into a 1 -L round-bottom flask, was placed 8-(benzyloxy)-l,4-dioxaspiro[4.5]decane (40 g, 161.08 mmol, 1.00 equiv), HC1 (6N, 400 mL, 2.50 equiv), tetrahydrofuran (300 mL). The resulting solution was stirred for 18 h at room temperature. The resulting solution was extracted with ethyl acetate (200mL x 3) and the organic layers combined and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/hexane (1 : 10). This resulted in 19.2 g (58percent) of 4-(benzyloxy)cyclohexan-l - one as yellow oil. MS (ES, m/z) [M+H]+: 205. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 6 h; Stage #2: at 20℃; Stage #3: With hydrogenchloride In tetrahydrofuran; water; mineral oil at 20℃; for 6 h; |
4-(Benzyloxy)cyclohexanone (14-2): A 60percent dispersion of sodium hydride in mineral oil (760 mg, 23 mmol, 1.2 equiv) was added to a solution of l ,4-Dioxaspiro[4.5]decan-8-ol (14-1) (3.0 g, 19 mmol, 1.0 equiv) in anhydrous THF (50 mL) at 0 °C. After 6 hours benzyl bromide (2.5 mL, 21.3 mmol, 1.1 equiv) was added to the mixture. The mixture was stirred at room temperature overnight. A 4N HCl solution (30 mL) was added and the reaction was stirred at room temperature for an additional 6 hours. The reaction was neutralized to pH ~7 with 4N sodium hydroxide and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified on an AnaLogix automated column chromatography system eluting with gradient of 0 to 30percent ethyl acetate in heptanes to give 14-2 (3.0 g, 77percent yield) as a light yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -40 - 0℃; | |
96% | With copper(II) permanganate In dichloromethane; acetic acid at 40 - 45℃; for 0.05h; | |
94% | With Oxone; sodium ortho-iodobenzenesulfonate; sodium sulfate In ethyl acetate at 70℃; for 8h; Inert atmosphere; |
94% | With Oxone; potassium 2-iodo-5-methylbenzenesulfonate; sodium sulfate In ethyl acetate at 70℃; for 8h; chemoselective reaction; | |
91% | With pyridinium chlorochromate In dichloromethane for 3h; Ambient temperature; | |
50% | With pyridinium chlorochromate In dichloromethane at 20℃; for 12h; Molecular sieve; | |
With chromium(VI) oxide; sulfuric acid In acetone | ||
With chromium(VI) oxide; acetic acid | ||
With pyridinium chlorochromate | ||
0.045 g | With chromium(VI) oxide; sulfuric acid In acetone at 20℃; for 0.0833333h; | |
With potassium dichromate; sulfuric acid | ||
With pyridinium chlorochromate In dichloromethane at 20℃; for 12h; | Step 2: To a solution of 4-(benzyloxy)cyclohexan-l-ol (7.00 g, 33.9 mmol) in DCM (140.0 mL) was added PCC (10.9 g, 50.9 mmol) and celatom (10.9 g) at ambient temperature. The resulting mixture was stirred for 12 h. The reaction mixture was filtered and washed with a saturated sodium bicarbonate solution (2x). The organic layer was concentrated under reduced pressure and the residue was purified by silica gel chromatography, eluting with a gradient of ethyl acetate : petroleum ether (1 : 5 to 1 : 3) to afford 4-(benzyloxy)cy cl ohexan-1- one. MS: 205 (M + H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In dichloromethane at -78 - 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ethylaluminum dichloride; diisobutylaluminium hydride In dichloromethane at -78℃; for 3h; other cycloalkanones, other reagents, var. temp.; influence of EtAlCl2; | ||
With ethylaluminum dichloride; diisobutylaluminium hydride In dichloromethane for 3h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; | ||
With diisobutylaluminium hydride In dichloromethane for 1h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; |
With sodium tetrahydroborate In methanol at 20℃; for 2.16667h; | 22.1; 23.1 To an ice-bath cooled solution of 4-(benzyloxy)cyclohexanone (31.0 g. 152 mmol) in 500 mL methanol, sodium horohydride (5.7 g, 153 mmol) was added in several potions during a period of 10 mm, then the solution was stirred at 20 °C for 2 h. Then the mixture was quenched by saturated aqueous soiuuon of ammoniuni chloride (50 mL), concentrated and the residue was dissolved in 20() rnL water and extracted with ethyl acetate (200 mL x 3). the combined organic phase was dried over sodium sulfate, then concentrated under vacuo to give title product (ir,4r)-4- (benzyioxy)cyclohexanol and (1 s,4s)-4-(benzyloxy)cyciohexanoi as a pale yellow oil (31.0 g, crude) which was used to nexL step directly withouL further punfication, . MS (ES+) C3H18O2 requires:206, found: 207[M±l-lit. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With CAN In water monomer; acetonitrile at 70℃; for 0.0333333h; | |
97% | With CAN In acetonitrile at 60 - 70℃; for 0.0333333h; | |
97% | With hydrogenchloride In 1,4-dioxane; water monomer at 40℃; for 20h; |
95.2% | With hydrogenchloride In tetrahydrofuran; water monomer at 20℃; | 2 To a solution of 1-ethylene acetal-4-benzyloxy-cyclohexane (17) (3.13 g, 12.6 mmol) in 50 ml THF, aqueous hydrochloric acid (1N, 30 ml) was added at rt. The reaction was stirred overnight and neutralized with sodium bicarbonate (sat.). The product was extracted with ethyl acetate and the organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by the silica gel chromatography (20% ethyl acetate in hexane) yielded 2.45 g (95.2%) of the title ketone. 1H NMR (CDCl3) δ: 1.95-2.62 (8H, m, 4×-CH2-), 3.82 (1H, m, -CH-), 4.59 (2H, s, Ph-CH2-), 7.28-7.36 (5H, m, Ph-H). |
94% | With hydrogenchloride In tetrahydrofuran for 3h; Heating; | |
93% | With hydrogenchloride In tetrahydrofuran; water monomer for 0.5h; Inert atmosphere; Reflux; | |
93% | With iron(III) trichloride hexahydrate; acetaldehyde In dichloromethane at 20℃; for 0.5h; chemoselective reaction; | |
92% | With acetic acid In tetrahydrofuran; water monomer at 75℃; for 18h; | |
80% | With acetic acid In tetrahydrofuran; water monomer at 75℃; for 18h; Inert atmosphere; | |
75% | With sulfuric acid In acetone Heating; | |
With water monomer; toluene-4-sulfonic acid In acetone for 72h; Yield given; | ||
With toluene-4-sulfonic acid for 1h; Heating; Yield given; | ||
With hydrogenchloride; Sodium hydrogenocarbonate In methanol; hexane; ethyl acetate | 4 4-Benzyloxycyclohexanone 41 4-Benzyloxycyclohexanone 41 A solution of 4-benzyloxy cyclohexanone ethylene ketal 40 (5.0 g, 20.1 mmol) in methanol (20 mL) and 1N HCl (0.5 mL) was stirred overnight at 25° C. (Step 37). The mixture was neutralized by addition of 1N NaHCO3 (0.5 mL), solvent removed by roto-evaporation, and the residue chromatographed on silica gel using 15:85 ethyl acetate/hexane. Yield of the ketone 41 was 2.7 g (67%); Rf=0.35; 1 H NMR (CDCl3) δ 2.3 (m, 8H, ring--CH2) 3.6 (m, 1H, CH--O), 4.6 (s, 2H, CH2 --O). | |
With hydrogenchloride; Sodium hydrogenocarbonate In methanol; hexane; ethyl acetate | 4 4-Benzyloxycyclohexanone 41 4-Benzyloxycyclohexanone 41 A solution of 4-benzyloxy cyclohexanone ethylene ketal 40 (5.0 g, 20.1 mmol) in methanol (20 mL) and 1N HCl (0.5 mL) was stirred overnight at 25° C. (Step 37). The mixture was neutralized by addition of 1N NaHCO3 (0.5 mL), solvent removed by roto-evaporation, and the residue chromatographed on silica gel using 15:85 ethyl acetate /hexane. Yield of the ketone 41 was 2.7 g STR8 (67%); Rf=0.35; 1 H NMR (CDCl3) δ2.3 (m, 8H, ring-CH2), 3.6 (m, 1H, CH--O), 4.6 (s, 2H, CH2 --O). | |
With hydrogenchloride; water monomer In tetrahydrofuran Reflux; | 1.3 Step 3:Preparation of 4-benzyloxy-cvclohexanone; 8-Benzyloxy-1 ,4-dioxa-spiro[4.5]decane (15g, 60 mmol) was dissolved in THF (150 ml) and 1M aqueous hydrochloric acid (40 ml) is added and the reaction mixture is heated to reflux overnight. The reaction mixture is cooled and diluted with water (200 ml) before being extracted with ethyl acetate (1 x 200 ml). The organic extract is washed with saturated solution of sodium bicarbonate and then dried over magnesium sulphate, filtered and evaporated under reduced pressure to give an oil. The oil is distilled under vacuum in a kugelrohr to give 4-benzyloxy-cyclohexanone (10g). | |
With hydrogenchloride In tetrahydrofuran; water monomer at 20℃; for 18h; | 4 4-(Benzyloxy)cyclohexanone (13-3): IN HC1 (60 mL) was added to a solution of 13-2 (9.15 g. 36.9 mmol) in THF (90 mL) and the mixture stirred at room temperature for 18 nr. The mixture was concentrated under reduced pressure to remove most of the THF. The residual aqueous oil was made alkaline by slow addition of saturated sodium bicarbonate and extracted with a 1 to 2 mixture of ethyl acetate and heptanes. The organic layer was washed with saturated brine (50 mL), dried over sodium sulfate, filtered and the filtrate concentrated under reduced pressure to give crude 13-3 (7.53 g) as a yellow oil. Crude 13-3 was used subsequently. | |
Stage #1: 8-(benzyloxy)-1,4-dioxaspiro[4.5]decane With hydrogenchloride In water monomer Stage #2: With sodium hydroxide In water monomer | ||
With hydrogenchloride In tetrahydrofuran; methanol at 20℃; for 16h; | 2 Step 2: 4-(benzyloxy)cyclohexanone Step 2: 4-(benzyloxy)cyclohexanone To a stirred solution of 8-(benzyloxy)-l,4-dioxaspiro[4.5]decane (32.4 g, 0.13 mol) in THF (200 mL) was added a solution of HC1 in MeOH (100 mL of a 4 M solution, 0.4 mol). The solution was stirred for 16 h at ambient temparature. The reaction was concentrated in vacuo, diluted with aqueous NaHC03, and extracted with teo portions of DCM. The combined DCM layers were dried with a2S04, filtered, and the solvent was removed in vacuo to give title. MS (M+H) +: 205. | |
19.2 g | With hydrogenchloride In tetrahydrofuran; water monomer at 20℃; for 18h; Inert atmosphere; | 125.2; 126.2 [53 1] Step 2. 4-(benzyloxy)cyclohexan-l-one [532] Into a 1 -L round-bottom flask, was placed 8-(benzyloxy)-l,4-dioxaspiro[4.5]decane (40 g, 161.08 mmol, 1.00 equiv), HC1 (6N, 400 mL, 2.50 equiv), tetrahydrofuran (300 mL). The resulting solution was stirred for 18 h at room temperature. The resulting solution was extracted with ethyl acetate (200mL x 3) and the organic layers combined and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/hexane (1 : 10). This resulted in 19.2 g (58%) of 4-(benzyloxy)cyclohexan-l - one as yellow oil. MS (ES, m/z) [M+H]+: 205. |
With hydrogenchloride In tetrahydrofuran; water monomer for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With sodium ethanolate In ethanol 0 deg C -> room temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane; water Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With chloroform; 3-chloro-benzenecarboperoxoic acid for 4h; Ambient temperature; | |
83% | With p-toluenesulfonic acid monohydrate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 23℃; for 24.1667h; | |
With 3-chloro-benzenecarboperoxoic acid In chloroform at 25℃; for 14h; | 2 A 100 g 1,4-hexanediol was dissolved in 1.4 L of a mixture of acetonitrile and water (7:3 by volume). A mixture of 45.4 g of sodium bromate and 16.5 g of ammonium cerium (IV) nitrate was slowly added. The reaction was maintained under reflux conditions for 90 min. Once acetonitrile was removed by rotary evaporation, the solution was diluted with 800 mL of water and continuously extracted with chloroform for 72 h. The organic solution was dried over magnesium sulfate. Finally chloroform was evaporated from the organic solution to yield 99.5 g of a colorless oil (4-hydroxycyclohexanone). 130 g of benzyl chloride were slowly added to a solution of 60 g of 4-hydroxycyclohexanone in 400 mL of triethylamine. The solution was left to react at 25 ° C. for 2 h. After removal of the solvent, the product was purified by column chromatography to yield 100 g of a white powder 4-benzylestercyclohexanone. To a solution of 20 g 3-chloroperoxybenzoic acid in 200 mL of chloroform was added a solution of 15 g of 4-benzylestercylohexanone in 100 mL of chloroform. The reaction proceeded at 25° C. for 14 h. The solution was passed through Celite, extracted with brine and water successively. The solution was dried over magnesium sulfate and the solvent evaporated. Finally, the product was re-crystallized from a solution of ethyl acetate:hexane (1:4) to yield 7 g of white powder, benzylester protected 4-hydroxylcaprolactone (p-CLOH). 50 mg of 1,6-hexandiol, 20 g of D,L lactide (DLL) monomer and 4 g of p-CLOH were dried by azeotropic distillation of toluene. The monomers were heated to 140° C. to add stannous octoate (0.5 mol %) under a blanket of argon. The reaction was left to proceed at 160° C. for 14 h. The resulting polymer poly(DLL-pCLOH) was dissolved in acetone, precipitated in methanol and dried under reduced pressure. The benzyl protecting group was removed by dissolving 10 g of poly(DLL-pCLOH) in 100 ml of anhydrous ethyl acetate and adding 0.8 g of tin(IV) chloride under a blanket of argon. The reaction proceeded at 25° C. for 90 min. The resulting polymer poly(DLL-CLOH) was precipitated in methanol and dried under reduced pressure. To 4 g of poly(DLL-CLOH) dissolved in 20 mL of predried dichloromethane, was added 1.5 eq. of dry pyridine and was cooled to -5° C. A solution of ethylene chlorophosphate (0.5 mg) in 5 mL of dry chloroform was added dropwise and reacted for 2 h at -5° C. The resultant solution was allowed to reach 25° C. and react for 4 more h. The resulting solution was diluted with 50 mL dichloromethane, and then extracted with distilled water and a 1 M solution of NaHCO3. The organic phase was dried with sodium sulfate and filtered to yield poly(DLL-CLP). 3 g of poly(DLL-CLP) were dissolved in 30 mL of dry acetonitrile and cooled to -10° C. Approximately 300 mL of trimethylamine was condensed into the pressure vessel, which was then slowly heated to 60° C. The solution was stirred for 45 h at this temperature. The resulting polymer, a copolymer of d,l-lactide and caprolactone bearing phosphorylcholine pendant groups (poly(DLL-CLPC)), was precipitated in methanol and dried under reduced pressure. |
With 3-chloro-benzenecarboperoxoic acid | ||
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Stage #1: 4,4-ethylenedioxycyclohexan-1-ol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 6h; Stage #2: benzyl bromide In tetrahydrofuran; mineral oil at 20℃; Stage #3: With hydrogenchloride In tetrahydrofuran; water; mineral oil at 20℃; for 6h; | 5 4-(Benzyloxy)cyclohexanone (14-2): A 60% dispersion of sodium hydride in mineral oil (760 mg, 23 mmol, 1.2 equiv) was added to a solution of l ,4-Dioxaspiro[4.5]decan-8-ol (14-1) (3.0 g, 19 mmol, 1.0 equiv) in anhydrous THF (50 mL) at 0 °C. After 6 hours benzyl bromide (2.5 mL, 21.3 mmol, 1.1 equiv) was added to the mixture. The mixture was stirred at room temperature overnight. A 4N HCl solution (30 mL) was added and the reaction was stirred at room temperature for an additional 6 hours. The reaction was neutralized to pH ~7 with 4N sodium hydroxide and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified on an AnaLogix automated column chromatography system eluting with gradient of 0 to 30% ethyl acetate in heptanes to give 14-2 (3.0 g, 77% yield) as a light yellow oil. |
(i) K, (ii) /BRN= 385801/, (iii) aq. AcOH; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: 4-(benzyloxy)cyclohexanone With lithium diisopropyl amide In tetrahydrofuran at -78℃; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at 0℃; for 2h; Further stages.; | |
72% | Stage #1: 4-(benzyloxy)cyclohexanone With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran; hexane at 0℃; for 1h; | |
59% | Stage #1: 4-(benzyloxy)cyclohexanone With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -78℃; for 1.25h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran; n-heptane; ethylbenzene at -78 - 20℃; | 1.D Intermediate D: 4-(Benzyloxy)cyclohex-l-en-l-yl trifluoromethanesulfonate To a stirred solution of LDA (2.0 M in THF/heptane/ethylbenzene) (36.6 mL, 73.2 mmol) in THF (60 mL) at -78°C was added 4-(benzyloxy)cyclohexanone (13.6 g, 66.6 mmol) dropwise over 15 minutes. The resulting solution was stirred at -78°C for 1 hour before the addition of a solution of l,l,l-trifluoro-/V-phenyl-/V-((trifluoromethyl)sulfonyl)methanesulfonamide (25.0 g, 69.9 mmol) in THF (60 mL) dropwise over 30 minutes. The reaction was stirred at -78°C for 1 hour, then allowed to slowly warm to room temperature overnight. The mixture was partitioned between EtOAc (100 mL) and water/saturated brine (1 : 1, 100 mL). The layers were separated and the aqueous extracted with EtOAc (3 x 50 mL). The organic extracts were combined and then dried over MgS04, filtered and concentrated in vacuo. The crude product was purified by chromatography on silica gel (330 g, 0-10% EtOAc in isohexane, gradient elution) to afford the title compound 4-(benzyloxy)cyclohex-l-en-l-yl trifluoromethanesulfonate (14.8 g, 59%) as a pale yellow oil. Analytical data: NMR (400 MHz, DMSO- is) d: 7.38 - 7.22 (5H, m), 5.79 (1H, t), 4.54 (1H, d), 4.51 (1H, d), 3.72 (1H, m), 2.54 - 2.38 (2H, m), 2.38 - 2.18 (2H, m), 1.96 - 1.81 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With toluene-4-sulfonic acid In methanol for 24h; | |
Stage #1: 4-(benzyloxy)cyclohexanone; trimethyl orthoformate With toluene-4-sulfonic acid In methanol Stage #2: With sodium hydrogencarbonate In methanol; dichloromethane; water | 58a 5.29 ml_ of trimethyl orthoformate and 32 mg of p-toluene sulfonic acid were added to a solution of 4-benzyloxy cyclohexanone in 20 ml_ of dry methanol and the mixture was stirred overnight. 20 ml_ of saturated aqueous sodium bicarbonate solution and 20 ml_ of dichloromethane were added, the aqueous layer was extracted several times with dichloromethane and the combined organic layers were dried and evaporated to dryness to yield 1.50 g of the desired product, which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sodium hydride In tetrahydrofuran; mineral oil at 80℃; for 2h; Cooling with ice; Inert atmosphere; | 1 Step 1 into a 250-inL round-bottom flask was placed a solution of 4-(benzyioxy)cyciohexan-1 -one(10.0 g, 48.96 mmol, 1.00 eq.) in THF (100 rnL). The flask was placed into ice bath, to the solution was added sodium hydride (2.35 g, 60% dispersion in mineral oil, 58.75 mmoi, 1.20 eq.) anddimethyl carbonate (6.62 g, 73.49 rnmol, 150 eq.) under N2 atmosphere. The resulting mixture was allowed to stir in an oil bath at 80 °C for 2 h. After cooling the reaction to room temperature, the reaction mixture was quenched with water and extracted with ethyl acetate thrice, The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide methyl 5-(henzyioxy)-2-oxocycl ohexane- I -carhoxyl ate as a colorless oil(12.5 g, 97%). LCMS (ES) [M+litm/z 263.1. |
85% | With sodium hydride In tetrahydrofuran Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 32 percent / NaH / dimethylformamide / 24 h 2: 99 percent / oxalyl chloride; DMSO; Et3N / CH2Cl2 / -40 - 0 °C | ||
Multi-step reaction with 2 steps 1: Na / tetrahydrofuran / 18 h / 40 - 50 °C 2: 0.045 g / CrO3; H2SO4 / acetone / 0.08 h / 20 °C | ||
Multi-step reaction with 2 steps 1: NaH 2: PCC |
Multi-step reaction with 2 steps 1: Na / toluene / Heating 2: CrO3, H2SO4 / acetone | ||
Multi-step reaction with 2 steps 1: (i) Na, xylene, (ii) /BRN= 385801/ 2: CrO3, AcOH | ||
Multi-step reaction with 2 steps 1: sodium hydride / N,N-dimethyl-formamide / 12 h / 20 °C 2: pyridinium chlorochromate / dichloromethane / 12 h / 20 °C / Molecular sieve |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: KH / tetrahydrofuran / 0 - 20 °C 1.2: 83 percent / tetrahydrofuran / 20 °C 2.1: 94 percent / aq. HCl / tetrahydrofuran / 3 h / Heating | ||
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) THF, 0 deg C, 2.) THF, reflux, 12 h 2: aq. p-TsOH / 1 h / Heating | ||
Multi-step reaction with 2 steps 1: 93 percent / NaH / tetrahydrofuran / Heating 2: 75 percent / 2 M aq. H2SO4 / acetone / Heating |
Multi-step reaction with 2 steps 1: 1.) KH / 1.) THF, 2.) 0 deg C, 30 min 2: p-toluenesulfonic acid, H2O / acetone / 72 h | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 2 h / 20 °C 1.2: 0.33 h / 20 °C 2.1: hydrogenchloride; water monomer / tetrahydrofuran / Reflux | ||
Multi-step reaction with 2 steps 1.1: potasssium hydride / tetrahydrofuran / 0.52 h / -16 - 20 °C / Inert atmosphere 1.2: 48 h / 20 °C / Inert atmosphere 2.1: hydrogenchloride / tetrahydrofuran; water monomer / 0.5 h / Inert atmosphere; Reflux | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 2.33 h / 5 - 45 °C 1.2: 20 - 25 °C 2.1: hydrogenchloride / water monomer; tetrahydrofuran / 18 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: potassium-t-butoxide / N,N-dimethyl-formamide 1.2: 0 °C 2.1: hydrogenchloride / water monomer | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h 1.2: 1 h / 0 °C 2.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 20 °C | ||
Multi-step reaction with 2 steps 1: sodium hydride / tetrahydrofuran; mineral oil / 24 h / 0 °C / Inert atmosphere 2: acetic acid / tetrahydrofuran; water monomer / 18 h / 75 °C | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 2.17 h / 20 °C 1.2: 20 h / 20 °C 2.1: hydrogenchloride / water monomer; 1,4-dioxane / 20 h / 40 °C | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.08 h / 0 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: hydrogenchloride / tetrahydrofuran; water monomer / 18 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: sodium hydride / tetrahydrofuran / 24 h / 0 °C 2: hydrogenchloride / tetrahydrofuran; water monomer / 6 h | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C / Inert atmosphere 1.2: 12 h / 70 °C / Inert atmosphere 2.1: acetic acid / tetrahydrofuran; water monomer / 18 h / 75 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: NaBH4 / methanol / 3 h / 0 °C 2.1: KH / tetrahydrofuran / 0 - 20 °C 2.2: 83 percent / tetrahydrofuran / 20 °C 3.1: 94 percent / aq. HCl / tetrahydrofuran / 3 h / Heating | ||
Multi-step reaction with 3 steps 1: 98 percent / LiAlH4 / tetrahydrofuran / Ambient temperature 2: 1.) NaH / 1.) THF, 0 deg C, 2.) THF, reflux, 12 h 3: aq. p-TsOH / 1 h / Heating | ||
Multi-step reaction with 3 steps 1.1: sodium tetrahydridoborate; methanol / 3 h / 5 - 20 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 2 h / 20 °C 2.2: 0.33 h / 20 °C 3.1: hydrogenchloride; water monomer / tetrahydrofuran / Reflux |
Multi-step reaction with 3 steps 1.1: sodium tetrahydridoborate / methanol / 3 h / 0 - 20 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: potasssium hydride / tetrahydrofuran / 0.52 h / -16 - 20 °C / Inert atmosphere 2.2: 48 h / 20 °C / Inert atmosphere 3.1: hydrogenchloride / tetrahydrofuran; water monomer / 0.5 h / Inert atmosphere; Reflux | ||
Multi-step reaction with 2 steps 1.1: sodium tetrahydridoborate; methanol / 3 h / 20 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 6 h / 0 °C 2.2: 20 °C 2.3: 6 h / 20 °C | ||
Multi-step reaction with 3 steps 1.1: sodium tetrahydridoborate; methanol / 3 h / 20 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 2.33 h / 5 - 45 °C 2.2: 20 - 25 °C 3.1: hydrogenchloride / water monomer; tetrahydrofuran / 18 h / 20 °C | ||
Multi-step reaction with 3 steps 1.1: sodium tetrahydridoborate / ethanol / 0 °C 2.1: potassium-t-butoxide / N,N-dimethyl-formamide 2.2: 0 °C 3.1: hydrogenchloride / water monomer | ||
Multi-step reaction with 3 steps 1.1: sodium tetrahydridoborate / methanol / 2 h / 0 °C 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h 2.2: 1 h / 0 °C 3.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 20 °C | ||
Multi-step reaction with 3 steps 1: sodium tetrahydridoborate / methanol / 1.5 h / 0 °C / Inert atmosphere 2: sodium hydride / tetrahydrofuran; mineral oil / 24 h / 0 °C / Inert atmosphere 3: acetic acid / tetrahydrofuran; water monomer / 18 h / 75 °C | ||
Multi-step reaction with 3 steps 1: sodium tetrahydridoborate; methanol / 12 h / 0 °C 2: sodium hydride / tetrahydrofuran / 24 h / 0 °C 3: hydrogenchloride / tetrahydrofuran; water monomer / 6 h | ||
Multi-step reaction with 3 steps 1.1: sodium hydride; sodium tetrahydridoborate / 0 °C / Inert atmosphere 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C / Inert atmosphere 2.2: 12 h / 70 °C / Inert atmosphere 3.1: acetic acid / tetrahydrofuran; water monomer / 18 h / 75 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: PPh3 / CH2Cl2 / 0.08 h / 0 °C 5: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, from -78 deg C to RT, 55 min 6: 98 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 7: 93 percent / H2, quinoline / Lindlar cat. / hexane / 1 h / 760 Torr / Ambient temperature 8: 57 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C 9: 1.) Bu3SnLi, 2.) NBu4F, 3.) MeMgBr, 1,1-diazodicarbonyldipiperidine, 4.) MgBr2*OEt2 | ||
Multi-step reaction with 7 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: 92 percent / CHCl3 / Ambient temperature 5: 95 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 6: 79 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C 7: 1.) Bu3SnLi, 2.) NBu4F, 3.) MeMgBr, 1,1-diazodicarbonyldipiperidine, 4.) MgBr2*OEt2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: PPh3 / CH2Cl2 / 0.08 h / 0 °C 5: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, from -78 deg C to RT, 55 min 6: 98 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 7: 93 percent / H2, quinoline / Lindlar cat. / hexane / 1 h / 760 Torr / Ambient temperature 8: 57 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C 9: 1.) Bu3SnLi, 2.) NBu4F, 3.) MeMgBr, 1,1-diazodicarbonyldipiperidine, 4.) MgBr2*OEt2 | ||
Multi-step reaction with 7 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: 92 percent / CHCl3 / Ambient temperature 5: 95 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 6: 79 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C 7: 1.) Bu3SnLi, 2.) NBu4F, 3.) MeMgBr, 1,1-diazodicarbonyldipiperidine, 4.) MgBr2*OEt2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: PPh3 / CH2Cl2 / 0.08 h / 0 °C 5: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, from -78 deg C to RT, 55 min 6: 98 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 7: 93 percent / H2, quinoline / Lindlar cat. / hexane / 1 h / 760 Torr / Ambient temperature 8: 57 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C 9: 1.) Bu3SnLi, 2.) NBu4F, 3.) MeMgBr, 1,1-diazodicarbonyldipiperidine, 4.) MgBr2*OEt2 | ||
Multi-step reaction with 7 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: 92 percent / CHCl3 / Ambient temperature 5: 95 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 6: 79 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C 7: 1.) Bu3SnLi, 2.) NBu4F, 3.) MeMgBr, 1,1-diazodicarbonyldipiperidine, 4.) MgBr2*OEt2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: PPh3 / CH2Cl2 / 0.08 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: PPh3 / CH2Cl2 / 0.08 h / 0 °C 5: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, from -78 deg C to RT, 55 min 6: 98 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: 92 percent / CHCl3 / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: PPh3 / CH2Cl2 / 0.08 h / 0 °C 5: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, from -78 deg C to RT, 55 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: PPh3 / CH2Cl2 / 0.08 h / 0 °C 5: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, from -78 deg C to RT, 55 min 6: 98 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 7: 93 percent / H2, quinoline / Lindlar cat. / hexane / 1 h / 760 Torr / Ambient temperature 8: 57 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C 9: 1.) Bu3SnLi, 2.) NBu4F, 3.) MeMgBr, 1,1-diazodicarbonyldipiperidine, 4.) MgBr2*OEt2 | ||
Multi-step reaction with 7 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: 92 percent / CHCl3 / Ambient temperature 5: 95 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 6: 79 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C 7: 1.) Bu3SnLi, 2.) NBu4F, 3.) MeMgBr, 1,1-diazodicarbonyldipiperidine, 4.) MgBr2*OEt2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: PPh3 / CH2Cl2 / 0.08 h / 0 °C 5: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, from -78 deg C to RT, 55 min 6: 98 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 7: 93 percent / H2, quinoline / Lindlar cat. / hexane / 1 h / 760 Torr / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: 92 percent / CHCl3 / Ambient temperature 5: 95 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: PPh3 / CH2Cl2 / 0.08 h / 0 °C 5: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, from -78 deg C to RT, 55 min 6: 98 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 7: 93 percent / H2, quinoline / Lindlar cat. / hexane / 1 h / 760 Torr / Ambient temperature 8: 57 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 95 percent / 80percent m-CPBA/CHCl3 / 4 h / Ambient temperature 2: 82 percent / DIBAL-H / toluene; CH2Cl2 / 1 h / -78 °C 3: 94 percent / Et3N / CH2Cl2 / 6 h / Ambient temperature 4: 92 percent / CHCl3 / Ambient temperature 5: 95 percent / DIBAL-H / CH2Cl2 / 1 h / -25 °C 6: 79 percent / CCl4, pyridine, PBu3 / 0.17 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) Na / 1.) dioxane, reflux, 4 h, 2.) dioxane, reflux, 20 h 2: 91 percent / PCC / CH2Cl2 / 3 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) Na / 1.) dioxane, reflux, 4 h, 2.) dioxane, reflux, 20 h 2: 91 percent / PCC / CH2Cl2 / 3 h / Ambient temperature | ||
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) THF, 0 deg C, 2.) THF, reflux, 12 h 2: aq. p-TsOH / 1 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 98 percent / HCl / ethanol / Heating 2: 85 percent / diethyl ether / Ambient temperature 3: DBU / tetrahydrofuran / 4 h / -5 °C | ||
Multi-step reaction with 2 steps 1: 63 percent / NaOEt / ethanol / 0 deg C -> room temperature 2: 1.) sodium hydride / 1.) THF, 0 deg C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 98 percent / HCl / ethanol / Heating 2: 85 percent / diethyl ether / Ambient temperature 3: DBU / tetrahydrofuran / 4 h / -5 °C 4: diethyl ether / -78 °C | ||
Multi-step reaction with 3 steps 1: 63 percent / NaOEt / ethanol / 0 deg C -> room temperature 2: 1.) sodium hydride / 1.) THF, 0 deg C 3: 41 percent / diethyl ether / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 93 percent / NaH / tetrahydrofuran / Heating 2: 75 percent / 2 M aq. H2SO4 / acetone / Heating | ||
Multi-step reaction with 2 steps 1: 1.) KH / 1.) THF, 2.) 0 deg C, 30 min 2: p-toluenesulfonic acid, H2O / acetone / 72 h | ||
Multi-step reaction with 2 steps 1.1: potassium hydride / tetrahydrofuran / 0.52 h / -16 - 20 °C / Inert atmosphere 1.2: 48 h / 20 °C / Inert atmosphere 2.1: hydrogenchloride / tetrahydrofuran; water / 0.5 h / Inert atmosphere; Reflux |
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h 1.2: 1 h / 0 °C 2.1: hydrogenchloride / tetrahydrofuran; methanol / 16 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 2.17 h / 20 °C 1.2: 20 h / 20 °C 2.1: hydrogenchloride / water; 1,4-dioxane / 20 h / 40 °C | ||
Multi-step reaction with 2 steps 1: sodium hydride / N,N-dimethyl-formamide / 12 h / 20 °C 2: pyridinium chlorochromate / dichloromethane / 12 h / 20 °C / Molecular sieve | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.08 h / 0 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: hydrogenchloride / tetrahydrofuran; water / 18 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 1)lithium diisopropylamide (LDA), 2) HMPA / 1)THF, -78 deg C to -25 deg C, 1.5 h, 2)THF, -25 deg C to 25 deg C, 3.75 h 2: 90 percent / NaIO4 / H2O; methanol / 12 h / 0 - 25 °C 3: t-BuOK/t-BuOH / tetrahydrofuran; 2-methyl-propan-2-ol / 1) 0-5 deg C, 22.5 h, 2) 25 deg C, 23 h 4: 61 percent / K2CO3 / acetone / 72 h / Heating 5: 98 percent / H2 (1 atm) / Pd/C / tetrahydrofuran / 24 h / 25 °C 6: 72 percent / Al(i-OPr)3 / toluene; cyclohexanone / 1.5 h / Heating | ||
Multi-step reaction with 6 steps 1: 1.) LDA / 1.) THF, -78 to 30 deg C, 1.5 h 2.) THF, HMPA, -30 to 25 deg C, 4.5 h 2: 88 percent / NaIO4 / methanol; H2O / 27 h / 0 - 25 °C 3: t-BuOK / 1.) THF, t-BuOH, 0 deg C, 22.5 h 2.) 25 deg C, 23 h 4: 60 percent / K2CO3 / acetone / 72 h / Heating 5: 98 percent / H2 / 10percent Pd/C / tetrahydrofuran / 24 h / 25 °C 6: 72 percent / Al(i-OPr)3, cyclohexanone / toluene / 1.5 h / 110 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 1)lithium diisopropylamide (LDA), 2) HMPA / 1)THF, -78 deg C to -25 deg C, 1.5 h, 2)THF, -25 deg C to 25 deg C, 3.75 h 2: 90 percent / NaIO4 / H2O; methanol / 12 h / 0 - 25 °C 3: t-BuOK/t-BuOH / tetrahydrofuran; 2-methyl-propan-2-ol / 1) 0-5 deg C, 22.5 h, 2) 25 deg C, 23 h 4: 61 percent / K2CO3 / acetone / 72 h / Heating 5: 98 percent / H2 (1 atm) / Pd/C / tetrahydrofuran / 24 h / 25 °C | ||
Multi-step reaction with 5 steps 1: 1.) LDA / 1.) THF, -78 to 30 deg C, 1.5 h 2.) THF, HMPA, -30 to 25 deg C, 4.5 h 2: 88 percent / NaIO4 / methanol; H2O / 27 h / 0 - 25 °C 3: t-BuOK / 1.) THF, t-BuOH, 0 deg C, 22.5 h 2.) 25 deg C, 23 h 4: 60 percent / K2CO3 / acetone / 72 h / Heating 5: 98 percent / H2 / 10percent Pd/C / tetrahydrofuran / 24 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 1.) n-butyllithium / 1.) THF, -78 deg C, 2.) -78 deg C, 2 h 2: p-toluenesulfonic acid / acetone / 48 h / Ambient temperature 3: Zn / diethyl ether / 3 h 4: Zn, NH4Cl / methanol / 16 h / Heating 5: molecular sieves 3A, pyridine / 24 h / 25 °C 6: 1.) p-toluenesulfonyl chloride, 2.) H2O / 1.) pyridine, RT, 6 h, 2.) RT, 46 h 7: 74.5 percent / BH3*THF / tetrahydrofuran / 1 h / Heating 8: 35 mg / H2, conc. HCl / 5percent Pd/C / ethanol / 3 h / 3102.9 Torr | ||
Multi-step reaction with 10 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 8: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr 9: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature 10: 68 percent / NaBH4 / methanol / 1 h / Heating | ||
Multi-step reaction with 10 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating 8: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature 9: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature 10: 68 percent / NaBH4 / methanol / 1 h / Heating |
Multi-step reaction with 8 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating 8: 19 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature | ||
Multi-step reaction with 11 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 7: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 8: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 9: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr 10: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature 11: 68 percent / NaBH4 / methanol / 1 h / Heating | ||
Multi-step reaction with 11 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 7: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 8: Raney nickel (W-2) / ethanol / 1 h / Heating 9: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature 10: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature 11: 68 percent / NaBH4 / methanol / 1 h / Heating | ||
Multi-step reaction with 9 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 7: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 8: Raney nickel (W-2) / ethanol / 1 h / Heating 9: 19 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature | ||
Multi-step reaction with 9 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 6: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 7: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr 8: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature 9: 68 percent / NaBH4 / methanol / 1 h / Heating | ||
Multi-step reaction with 9 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 6: Raney nickel (W-2) / ethanol / 1 h / Heating 7: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature 8: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature 9: 68 percent / NaBH4 / methanol / 1 h / Heating | ||
Multi-step reaction with 7 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 6: Raney nickel (W-2) / ethanol / 1 h / Heating 7: 19 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature | ||
Multi-step reaction with 10 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 8: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr 9: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature 10: 68 percent / NaBH4 / methanol / 1 h / Heating | ||
Multi-step reaction with 10 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating 8: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature 9: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature 10: 68 percent / NaBH4 / methanol / 1 h / Heating | ||
Multi-step reaction with 8 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating 8: 19 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 1.) n-butyllithium / 1.) THF, -78 deg C, 2.) -78 deg C, 2 h 2: p-toluenesulfonic acid / acetone / 48 h / Ambient temperature 3: Zn / diethyl ether / 3 h 4: Zn, NH4Cl / methanol / 16 h / Heating 5: molecular sieves 3A, pyridine / 24 h / 25 °C 6: 1.) p-toluenesulfonyl chloride, 2.) H2O / 1.) pyridine, RT, 6 h, 2.) RT, 46 h 7: 74.5 percent / BH3*THF / tetrahydrofuran / 1 h / Heating 8: 50 mg / H2, conc. HCl / 5percent Pd/C / ethanol / 3 h / 3102.9 Torr | ||
Multi-step reaction with 8 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 8: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr | ||
Multi-step reaction with 8 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating 8: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature |
Multi-step reaction with 9 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 7: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 8: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 9: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr | ||
Multi-step reaction with 9 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 7: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 8: Raney nickel (W-2) / ethanol / 1 h / Heating 9: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature | ||
Multi-step reaction with 7 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 6: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 7: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr | ||
Multi-step reaction with 7 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 6: Raney nickel (W-2) / ethanol / 1 h / Heating 7: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature | ||
Multi-step reaction with 8 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 8: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr | ||
Multi-step reaction with 8 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating 8: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 8: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr 9: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature | ||
Multi-step reaction with 9 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating 8: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature 9: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature | ||
Multi-step reaction with 10 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 7: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 8: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 9: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr 10: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature |
Multi-step reaction with 10 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 7: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 8: Raney nickel (W-2) / ethanol / 1 h / Heating 9: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature 10: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature | ||
Multi-step reaction with 8 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 6: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 7: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr 8: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature | ||
Multi-step reaction with 8 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 6: Raney nickel (W-2) / ethanol / 1 h / Heating 7: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature 8: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature | ||
Multi-step reaction with 9 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: 81 percent / boran-THF complex / tetrahydrofuran / 1 h / Heating 8: 68 percent / hydrogen, conc. HCl / 5percent Pd/C / ethanol / 24 h / 2942.03 Torr 9: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature | ||
Multi-step reaction with 9 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating 8: 71 percent / AlCl3, LiAlH4 / diethyl ether; tetrahydrofuran / 1 h / Ambient temperature 9: 62 percent / Jones reagent / acetone / 0.17 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating | ||
Multi-step reaction with 8 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 100 percent / potassium carbonate / methanol / 2 h / Ambient temperature 4: 78 percent / methanol / 7 h / 100 °C 5: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 6: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 7: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 8: Raney nickel (W-2) / ethanol / 1 h / Heating | ||
Multi-step reaction with 6 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 8 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 6: Raney nickel (W-2) / ethanol / 1 h / Heating |
Multi-step reaction with 7 steps 2: 83 percent / N-bromosuccinimide, water / acetonitrile / 1 h / Ambient temperature 3: 83 percent / methanol / 7 h / 100 °C 4: 79 percent / triethylamine / CH2Cl2 / 1 h / Ambient temperature 5: 80 percent / p-toluenesulfonic acid monohydrate / benzene / 1 h / Heating 6: 51 percent / tributyltin hydride, azobis(isobutyronitrile) / toluene / Heating 7: Raney nickel (W-2) / ethanol / 1 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: toluene / Heating 2: (+)-monoperoxycamphoric acid ((+)-MPCA) / toluene / 0.33 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: toluene / Heating 2: m-chloroperoxybenzoic acid (mCPBA) / toluene / 0.33 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: toluene / Heating 2: m-chloroperoxybenzoic acid (mCPBA) / toluene / 0.33 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: toluene / Heating 2: m-chloroperoxybenzoic acid (mCPBA) / toluene / 0.33 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: toluene / Heating 2: m-chloroperoxybenzoic acid (mCPBA) / toluene / 0.33 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: trimethylsilyl cyanide; 4-(benzyloxy)cyclohexanone With zinc(II) iodide In toluene at 0 - 20℃; for 2h; Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran; toluene at 0 - 20℃; for 2h; Stage #3: With hydrogenchloride; water more than 3 stages; | 24 4- (Benzyloxy) cyclohexanone (19 g, 94 mmol) (J. Org. Chemin. 1982, 47, 3881-3886.) was added dropwise to a mixture of Znk (1.5 g, 4.7 mmol) and TMSCN (13 mL, 98 mmol) in toluene (100 mL) at 0 °C and the mixture was stirred at room temperature for 2 hours. The mixture was dropwised to a suspension of LiAIH4 (8.5 g, 98 mmol) in THF (400 mL) at 0 °C and the mixture was stirred at room temperature for 2 h. The mixture was quenched with Na2SO4-10H2O (excess) and stirred for 4 hours. After filtration, the filtrate was evaporated. The residue was dissolved with ethanol and 4N HCI in AcOEt (25 mL) was added at 0 °C. The sovent was removed in vacuum. The residue was crystallized from ethanol to afford the titled compound (6.1 g) as a white solid. 1H NMR (DMSO-d6) 6 : 8.00 (br, 3H), 7.40-7. 20 (m, 5H), 4.91 (br, 1H), 4. 82-4. 44 (m, 2H), 3.60-3. 24 (m, 1H), 2.80-2. 65 (m, 2H), 1. 85-1. 20 (m, 8H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trimethylamine at 25℃; for 2h; | 2 A 100 g 1,4-hexanediol was dissolved in 1.4 L of a mixture of acetonitrile and water (7:3 by volume). A mixture of 45.4 g of sodium bromate and 16.5 g of ammonium cerium (IV) nitrate was slowly added. The reaction was maintained under reflux conditions for 90 min. Once acetonitrile was removed by rotary evaporation, the solution was diluted with 800 mL of water and continuously extracted with chloroform for 72 h. The organic solution was dried over magnesium sulfate. Finally chloroform was evaporated from the organic solution to yield 99.5 g of a colorless oil (4-hydroxycyclohexanone). 130 g of benzyl chloride were slowly added to a solution of 60 g of 4-hydroxycyclohexanone in 400 mL of triethylamine. The solution was left to react at 25 ° C. for 2 h. After removal of the solvent, the product was purified by column chromatography to yield 100 g of a white powder 4-benzylestercyclohexanone. To a solution of 20 g 3-chloroperoxybenzoic acid in 200 mL of chloroform was added a solution of 15 g of 4-benzylestercylohexanone in 100 mL of chloroform. The reaction proceeded at 25° C. for 14 h. The solution was passed through Celite, extracted with brine and water successively. The solution was dried over magnesium sulfate and the solvent evaporated. Finally, the product was re-crystallized from a solution of ethyl acetate:hexane (1:4) to yield 7 g of white powder, benzylester protected 4-hydroxylcaprolactone (p-CLOH). 50 mg of 1,6-hexandiol, 20 g of D,L lactide (DLL) monomer and 4 g of p-CLOH were dried by azeotropic distillation of toluene. The monomers were heated to 140° C. to add stannous octoate (0.5 mol %) under a blanket of argon. The reaction was left to proceed at 160° C. for 14 h. The resulting polymer poly(DLL-pCLOH) was dissolved in acetone, precipitated in methanol and dried under reduced pressure. The benzyl protecting group was removed by dissolving 10 g of poly(DLL-pCLOH) in 100 ml of anhydrous ethyl acetate and adding 0.8 g of tin(IV) chloride under a blanket of argon. The reaction proceeded at 25° C. for 90 min. The resulting polymer poly(DLL-CLOH) was precipitated in methanol and dried under reduced pressure. To 4 g of poly(DLL-CLOH) dissolved in 20 mL of predried dichloromethane, was added 1.5 eq. of dry pyridine and was cooled to -5° C. A solution of ethylene chlorophosphate (0.5 mg) in 5 mL of dry chloroform was added dropwise and reacted for 2 h at -5° C. The resultant solution was allowed to reach 25° C. and react for 4 more h. The resulting solution was diluted with 50 mL dichloromethane, and then extracted with distilled water and a 1 M solution of NaHCO3. The organic phase was dried with sodium sulfate and filtered to yield poly(DLL-CLP). 3 g of poly(DLL-CLP) were dissolved in 30 mL of dry acetonitrile and cooled to -10° C. Approximately 300 mL of trimethylamine was condensed into the pressure vessel, which was then slowly heated to 60° C. The solution was stirred for 45 h at this temperature. The resulting polymer, a copolymer of d,l-lactide and caprolactone bearing phosphorylcholine pendant groups (poly(DLL-CLPC)), was precipitated in methanol and dried under reduced pressure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium hydroxide In methanol; diethyl ether; nitrobenzene | 18 6-Chloro-2-benzyloxy-1,2,3,4-tetrahydro-9-acridinamine EXAMPLE 18 6-Chloro-2-benzyloxy-1,2,3,4-tetrahydro-9-acridinamine To a mechanically stirred solution of 4-benzyloxycyclohexanone (J Chem. Soc., Chem Commum. 1984 , 721.) (10.77 g) and 4-chloroanthranilonitrile (J. Amer. Chem. Soc. 1947 , Volume 69, 940.) (7.93 g) in nitrobenzene (72.6 ml) was added freshly fused zinc chloride (7.9 g). The reaction mixture was heated at 60°C for 90 minutes and thereafter at 120°C for three hours. The reaction mixture was cooled to room temperature, anhydrous diethyl ether (170 ml) was added dropwise, and the precipitate was filtered, washed well with diethyl ether and dissolved in methanol (200 ml). Saturated ammonium hydroxide (200 ml) was added dropwise while the mixture was cooled in an ice bath. The resulting solid was filtered, washed successively with deionized water and diethyl ether and air dried to yield 7.2 g of a white solid. A 4.86 g portion was recrystallized from ethanol/hexane and dried under high vaccum with the aid of refluxing xylenes to yield 3.5 g of product; mp 220° (dec.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With ammonium chloride; potassium hexamethylsilazane In tetrahydrofuran; hexane; ethyl acetate; toluene | 20.4 4. 4. E-4-(4-Benzyloxycyclohexylidene)but-2-enoic acid ethyl ester A stirred, cooled (-78° C.) solution of triethyl phosphonocrotonate (28.3 ml, 0.128 mol) in anhydrous tetrahydrofuran (350 ml), under a nitrogen atmosphere, was treated with a 0.5M toluene solution of potassium bis(trimethylsilyl)amide (240 ml, 0.12 mol) dropwise over 30 minutes. The dark orange solution was stirred at -78° C. for 5 hours then treated slowly with a solution of 4-benzyloxycyclohexanone (16.3 g, 0.08 mol) in anhydrous tetrahydrofuran (50 ml). The reaction mixture was stirred at -78° C. for 2 hours then stirred whilst warming to room temperature overnight. The mixture was quenched with saturated ammonium chloride solution (250 ml) then the tetrahydrofuran was evaporated and the aqueous was extracted with ethyl acetate (3*200 ml). The combined organics were washed with brine, dried (sodium sulphate) then evaporated to dryness. The residue was purified by column chromatography on silica using ethyl acetate/n-hexane (1:5) to afford the diene as a colourless oil (22.0 g, 92%). MS, ES+, m/z=301 for (M+H)+; δ(250 MHz, CDCl3) 1.30 (3H, t, J=7 Hz), 1.62-1.80 (2H, m), 1.84-2.00 (2H, m), 2.06-2.34 (2H, m), 2.40-2.54 (1H, m), 2.64-2.80 (1H, m), 3.59-3.66 (1H, m), 4.20 (2H, q, J=7 Hz), 5.81 (1H, d, J=15 Hz), 5.97 (1H, d, J=12 Hz), 7.26-7.37 (5H, m), 7.60 (1H, dd, J1=12, J2=15 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane; <i>tert</i>-butyl alcohol at 0 - 20℃; for 5.16667h; | 214.A To a solution of 4-(benzyloxy)cyclohexanone (2.94 g, 14.39 mmol, prepared according to procures described in Goodman et al., U.S. Patent Application Publication No. 2006/0292073 A1) in 1,2-dimethoxyethane (14.39 mL, Aldrich) was added tosylmethyl isocyanide (5.62 g, 28.8 mmol, Aldrich) in one portion. The resulting mixture was cooled to 0° C. and potassium t-butoxide solution (3.82 mL, 3.82 mmol, 1.0 M in 2-methyl-2-propanol, Aldrich) was added dropwise. The reaction mixture was stirred at 0° C. for 10 min and at room temperature for 5 hrs and then quenched with 1N HCl (45 mL). The aqueous layer was extracted further with EtOAc (3×). The combined organic extracts were washed with brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (0-40% EtOAc/hexanes) to give a cis and trans mixture of 4-(benzyloxy)cyclohexanecarbonitrile (2.14 g, 69%) as a light orange oil. MS (EST) 216 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With boron trifluoride diethyl etherate In dichloromethane at -78℃; for 0.5h; Inert atmosphere; optical yield given as %de; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: ethyl 2-((tert-butyldimethylsilyl)oxy)-2-(diethoxyphosphoryl)acetate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 4-(benzyloxy)cyclohexanone In tetrahydrofuran at -78 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,4-dioxane; water at 20℃; for 48h; | 30.1 To a mixture of 4-(benzyloxy)cyclohexanone (14.3 g} 70.2 mmol) (synthesized in accordance with the procedure in US 2006292073, pages 11-12) methylamine hydrochloride (19.0 g, 280 mmol), and sodium cyanide (17.8 g, 280 mmol) in a 1 :1 mixture of dioxane:water (150 mL) was stirred at room temperature for 48 hours. The reaction mixture was concentrated under vacuum. The residue was partitioned between ethyl acetate and water. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to afford the intermediate 4-(benzyloxy)-l-(methylamrao)cyclohexanecarbomtrile as a mixture of cis and trans isomers. A solution of the aminocyclohexanecarbonitrile (16.8 g, 68.8 mmol) and di-tert-butyl dicarbonate (45 g, 206 mmol) in dioxane (250 mL) was heated at 400C for 6 days. The product mixture was concentrated under vacuum, and the residue partitioned between ethyl acetate and water. The organic extract was dried over sodium sulfate, filtered, and concentrated under vacuum. The -1:1 mixture of faster and slower eluting diastereoisomers was separated by column chromatography on silica gel eluting with a 0% to 50% ethyl acetate/hexane gradient. Collection and concentration of faster eluting isomer afford white solid. Collection and concentration of slower eluting fractions afforded colorless oil. 1H NMR of faster eluting isomer (400 MHz, CDCI3): δ 7.37-733 (m, 5H); 4.50 (s, 2 H); 3.68 (br signal, 1 H); 2.92 (s, 3 H); 2.22-2.01 (m, 8 H); 1.51 (s, 9 H). 1H NMR of slower eluting isomer (400 MHz, CDCI3): δ 7.38-7.32 (m, 5 H); 4.56 (s, 2 H); 3.36 (m, 1 H); 2.92 (s, 3 H); 2.75-1.73 (sets of multiplets); 1.52 (s, 9 H). Both isomers were carried through the following reaction sequence. Precursor derived from the faster eluting isomer underwent base induced cyciization to form the diazatricyclododecane core, while the corresponding intermediate derived from the slower eluting isomer did not. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: ammonium carbonate; 4-(benzyloxy)cyclohexanone With ammonium chloride In ethanol; water at 20℃; for 0.25h; Stage #2: potassium cyanide In ethanol; water at 20℃; | 2 To a solution of 4-benzyloxy-cyclohexanone (18) (2.45 g, 12 mmol) in 100 ml of ethanol was added a solution of ammonium carbonate (4.6 g, 48 mmol) and ammonium chloride (1.28 g, 24 mmol) in 100 ml of water. The mixture was stirred at rt for 15 min and then potassium cyanide (940 mg, 14.4 mmol) was added. The reaction was stirred at rt overnight. The solvent was removed under reduced pressure. The resulting solid was washed repeatedly with water and collected by filtration. This crude syn/anti mixture of hytantoins (3.02 g, 91.8%) was used without further purification. 1H NMR (CD3OD) δ: 1.58-2.15 (8H, m, 4×-CH2-), 3.48, 3.66 (1H, m, -CH-), 4.52, 4.56 (2H, s, Ph-CH2-), 7.25-7.33 (5H, m, Ph-H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: (methoxymethyl)triphenylphosphonium chloride With lithium diisopropyl amide In tetrahydrofuran; hexane; ethylbenzene at 0 - 5℃; for 0.5h; Stage #2: 4-(benzyloxy)cyclohexanone In tetrahydrofuran at -78 - 20℃; Stage #3: With hydrogenchloride; water at 20℃; for 3h; | 1.4 Step 4:Preparation of 4-benzyloxy-cvclohexanecarbaldehvde; To a stirred suspension of methoxymethyl triphenylphosphonium chloride (13.8 g, 40 mmol) in dry THF (80 ml) is added dropwise a solution of lithium diisopropylamide (24.4 ml, 44 mmol, 1.8 M in hexane / THF / ethylbenzeϖe), at 0-5 °C. The resulting reaction mixture is stirred for 30 minutes and then cooled to -78 0C. At this temperature, a solution of 4-benzyloxy-cyclohexanone (6.1 g, 30 mmol) in tetrahydrofuran (30ml) is added over a period of 30 minutes. Once the addition is completed the reaction mixture is stirred at -78 0C for 1 hour and then allowed to warm to room temperature and stirred overnight. The reaction mixture is then diluted to pH=2 with a 2N aqueous solution of hydrochloric acid and stirred for 3 hours at room temperature. The reaction was diluted with water and extracted with ethyl acetate (2 x 100 ml). The combined organic extracts are dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue is purified by flash chromatography to give 4-benzyloxy-cyclohexanecarbaldehyde (5.7g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium tetrahydroborate In tetrahydrofuran; methanol for 0.583333h; | |
With methanol; sodium tetrahydroborate at 0 - 20℃; for 3h; | 17.2 Step 2. Preparation of 4-(benzyloxy)cyclohexanol According to the similar procedure of steps 2 & 3 in Example 3, the desired product was obtained. 1H-NMR (400 MHz, CDCl3) δ 1.65 (8H, m), 3.40-3.49 (1H, m), 3.67 (1H, m), 4.52 (2H, d, J=8.8 Hz), 7.24-7.31 (5H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: 4-(benzyloxy)cyclohexanone With pyrrolidine In benzene for 5h; Reflux; Stage #2: acrylonitrile In 1,4-dioxane Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium azide; tetrachlorosilane In acetonitrile at 20℃; for 20h; | 4 7-(Benzyloxy)-6,7,8,9-tetrahydro-5H-tetrazolo[l,5-«]azepine (13-4):Sodium azide (5.95 g, 91.5 mmol, 3.0 equiv) was added to a solution of crude 13-3 (6.22 g, 20.5 mmol, 1.0 equiv) in acetonitrile (120 mL). Silicon tetrachloride (3.6 mL, 30.5 mmol, 1.0 equiv) was added dropwise to the suspension and the mixture stirred at room temperature with the suspension becoming thicker. After ~20 hours, the thick yellow suspension was poured slowly into cold (~5 °C) 10% sodium carbonate (700 mL). The suspension was extracted with ethyl acetate (3 x 200 mL, 1 x 100 mL) - some insolubles remained in the aqueous phase. The combined organic layers were washed with saturated brine (2 x 150 mL), dried over sodium sulfate, filtered and the filtrate concentrated under reduced pressure to give a tan solid. TLC (50% ethyl acetate in heptanes, Hanessian's stain) showed 13-3, some higher R/ impurities and baseline material. The crude product was dissolved in ethyl acetate (250 mL), silica gel (5 g) and charcoal (0.7 g) were added and the solution stirred at 40 °C for 0.25 hr. The mixture was filtered through a CELITE pad, washing the pad with ethyl acetate (400 mL). The filtrate was concentrated under reduced pressure to give a light tan solid. The crude product was purified on an ANALOGIX automated chromatography system eluting with 0 to 5% methanol in dichloromethane to give 13-4 (4.12 g, -91% purity by LCMS) as an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With water-d2; C12H12F6O4Pt at 80℃; for 8h; Sealed tube; | |
98% | With chloroform-d1; 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine at 20℃; Reflux; | 5 4-(Benzyloxy)-2,2,6,6-d4-cyclohexanone (14-3): Triazabicyclodecene (TBD) (200 mg, 1.44 mmol, 0.1 equiv) was added to a solution of4-(Benzyloxy)cyclohexanone (14-2) (3.0 g, 14.7 mmol, 1.0 equiv) was dissolved in chloroform-d (50 mL). The mixture was stirred at room temperature overnight, at which point-NMR showed 85 % deuterium incorporation. The mixture was then refluxed for 6 hours, at which point-NMR showed deuterium exchange was complete. The reaction was cooled to room temperature and washed sequentially with IN HCl (20 mL), water, and saturated brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give 14-3 (3.0 g, 98% yield) as a light-yellow oil which was used subsequently. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 47% 2: 24% | Stage #1: tert-butyl (2S)-2-(2'-oxopropyl)pyrrolidine-1-carboxylate With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; Stage #2: 4-(benzyloxy)cyclohexanone With 2,2,2-trifluoroethyl trifluoromethanesulphonate In tetrahydrofuran at 20℃; for 72h; Inert atmosphere; Stage #3: With sodium tetrahydroborate In tetrahydrofuran; methanol at 0 - 20℃; for 3h; Inert atmosphere; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With bromine In diethyl ether for 1h; Cooling with ice; | D321 cis/trans-4-(benzyloxy)-2-bromocyclohexanone (D32 1) To a cooled solution of 4-(benzyloxy)cyclohexanone (8.4 g, 41.1 mmol) in diethyl ether (200 mL) was added bromine (2.119 mL, 41.1 mmol) under ice-water cooling. After stirred for 1 h, saturated aq. sodium thiosulfate was added and the mixture was extracted with ethyl acetate. The combined organic phases were dried, concentrated and purified by flash chromaography on silica gel (15-25% EA in PE) to give the title compound D321 (10 g, 35.3mmol, 86 % yield).LCMS: 305 [M+Na]. tR 3.537 mins. (LCMS condition 1) |
With N-Bromosuccinimide; toluene-4-sulfonamide In dichloromethane at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; acetic acid at 0℃; for 1.5h; | 3 Step 3: methyl 2-(4-(benzyloxy)cyclohexylidene)-2-cyanoacetate Step 3: methyl 2-(4-(benzyloxy)cyclohexylidene)-2-cyanoacetate Acetic acid (635 mg, 8.6 mmol) was added to a stirred mixture of 4- (benzyloxy)cyclohexanone (21.6 g, 106 mmol) and ethyl cyanoacetate (12 g, 106 mmol) at 0 °C, followed by piperidine (900 mg, 8.6 mmol). The ice-water bath was removed and 8.6 mmol portions each of acetic acid and piperidine were added. The mixture was stirred for 1.5 h, then partitioned between ethyl acetate and saturated NaHC03. The organic phase was separated and washed with brine, dried over a2S04, and concentrated in vacuo. The crude product was dissolved in ethyl acetate and precipitated with the addition of petroleum ether to give the title compound. MS (M+H)+: 300. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-(benzyloxy)cyclohexanone With sodium tetrahydroborate In methanol at 20℃; for 2.16667h; Stage #2: With trifluoromethylsulfonic anhydride; N-ethyl-N,N-diisopropylamine In dichloromethane at 25℃; for 18h; | 22.2; 23.2 To an ice-bath cooled solution of (lr,4r)-4-(benzyloxy)cyclohexanol and (ls,4s)-4- (benzyloxy)cyclohexanol (30.0 g, 145 mmol) and N,N-Diisopropylethylamine (28.1 g, 218 mmol) in 1200 mL dichloromethane, trifluoromeihanesulfonic anhydride (30.7 g, 109 mmol) was added dropwise during a period of 30 min, then the solution was stirred at 25 °C for 18 h. Then the mixture was concentrated under vacuo and the residue was purified with silica gel column chromatography, el u ting with petroleum ethenethyl acetate = 12:1 to give the title compound (28.0 g, yield 100%) as a yellow oil. MS (ES+) C13Hi60 requires: 188, found: 189 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With triethylamine tris(hydrogen fluoride); triethylamine; ethanaminium,N-(difluoro-λ4-sulfanylidene)-N-ethyl-,tetrafluoroborate In N,N-dimethyl acetamide at 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | Stage #1: 4-(benzyloxy)cyclohexanone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; Stage #2: N,N-diphenyltrifluoromethanesulfonamide In tetrahydrofuran at 20℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: diethyl (N-methoxy-N-methylcarbamoylmethyl)phosphonate With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 1.5h; Stage #2: 4-(benzyloxy)cyclohexanone In tetrahydrofuran at -78 - 20℃; for 16h; | 302 Example 302 (General Procedure X) To a cooled (0°C) solution of potassium tert-butoxide (4.6 g, 41 mmol) in tetrahydrofuran (50 mL) was added 2-diethoxyphosphoryl-N-methoxy-N-methyl-acetamide (10 g, 43 mmol). The mixture was allowed to warm to room temperature over30 mins and stirred for an additional 1 h. The mixture was cooled to -78°C, and a solutionof 4-benzyloxycyclohexanone (7.9 g, 39 mmol, 1.0 equiv) tetrahydrofuran (50 mL) wasadded. The mixture was allowed to slowly warm to room temperature and was stirred for16 h. The mixture was diluted with water (250 mL) and extracted with isopropyl acetate(3 x 100 mL). The combined organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with a gradient of 0 to 70% isopropyl acetate in heptane. The appropriate fractions were combined and concentrated under reduced pressure to afford 10 g (89%) of 2-(4-benzyloxycyclohexylidene)-N-methoxy-N-methyl-acetamide as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-(benzyloxy)cyclohexanone With sodium methylate In toluene at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: formic acid ethyl ester In toluene at 0 - 20℃; Inert atmosphere; | 125.3; 126.3 [533] Step 3. 5-(benzyloxy)-2-oxocyclohexane-l-carbaldehyde [534] Into a 500-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 4-(benzyloxy)cyclohexan-l-one (19 g, 93.02 mmol, 1.00 equiv), toluene (150 mL), MeONa (15.1 g, 3.00 equiv) was added with stirring at 0 °C. The above mixture was stirred for 5min at 0 °C. A solution of ethyl formate (41.4 g, 558.87 mmol, 6.00 equiv) was added slowly at 0 °C. The temperature was increased to room temperature naturally. The resulting solution was stirred for 12 h at room temperature. The reaction was then quenched by the addition of water/ice (300mL). The pH value of the solution was adjusted to 4 with hydrogen chloride (1 mol/L). The resulting solution was extracted with ethyl acetate (300mLx3) and the organic layers combined, dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 25 g (crude) of 5-(benzyloxy)-2-oxocyclohexane-l - carbaldehyde as yellow oil. MS (ES, m/z) [M+H]+: 233. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: Methyltriphenylphosphonium bromide With n-butyllithium In tetrahydrofuran at -10℃; for 1h; Inert atmosphere; Stage #2: 4-(benzyloxy)cyclohexanone In tetrahydrofuran at 20℃; for 3h; | 243.1 Step 1: (((4-Methylenecyclohexyl)oxy)methyl)benzene To a mixture of methyl (triphenyl)phosphonium bromide (10.5 g, 29.4 mmol, 1.5 eq) in anhydrous THF (70 mL) at -10° C. under N2 was added n-BuLi (2.5 M solution in hexanes, 11.0 mL, 27.4 mmol, 1.4 eq) and the mixture was stirred at -10° C. for 1 h. A solution of 4-benzyloxycyclohexanone (4.0 g, 19.6 mmol, 1.0 eq) in THF (10 mL) was then added dropwise and the mixture was allowed to warm to RT and stirred for 3 h. The reaction was quenched with water (100 mL) and the mixture was extracted with EtOAc (80 mL*3). The combined organic extracts were washed with brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether/EtOAc, 1:0 to 20:1, v/v) to afford the title compound (3.4 g, 86%) as a colorless oil. 1HNMR (400 MHz, CDCl3) δ 7.29-7.17 (m, 5H), 4.56 (s, 2H), 4.49 (s, 2H), 3.49-3.45 (m, 1H), 2.33-2.27 (m, 2H), 2.00-1.94 (m, 2H), 1.85-1.82 (m, 2H), 1.58-1.49 (m, 2H). |
65% | With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With sodium hydride In N,N-dimethyl-formamide at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium ethanolate In tetrahydrofuran; ethanol at 0 - 20℃; for 0.25h; Inert atmosphere; Stage #2: 4-(benzyloxy)cyclohexanone In tetrahydrofuran; ethanol for 0.5h; | Synthesis of (((4-(2-bromoethylidene)cyclohexyl)oxy)methyl)benzene (65) To a solution of 20% EtONa in EtOH (7.50 g, 22.0 mmol) and THF (24 ml) was added dropwise triethyl phosphonoacetate (4.37 ml, 22.0 mmol) at 0 °C under a nitrogen atmosphere. After stirring at the same temperature for 15 min, a solution of 4-(benzyloxy)cyclohexanone (45) (3.00 g, 14.7 mmol) in THF (12 ml) was added dropwise to the reaction mixture at the same temperature. After stirring at room temperature for 30 min, EtOAc (30 ml) and 5% KHSO4 aqueous solution (10 ml) were poured into the reaction mixture. The organic layer was washed with saturated NaHCO3 aqueous solution and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (hexane-EtOAc) to give ethyl 2-(4-(benzyloxy)cyclohexylidene)acetate (3.70 g, 92%) as a pale yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 10% 2: 11% | Stage #1: (methoxymethyl)triphenylphosphonium chloride With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 4-(benzyloxy)cyclohexanone In tetrahydrofuran at 0 - 20℃; Stage #3: With hydrogenchloride In tetrahydrofuran; water at 0℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | In methanol at 20℃; for 1h; Inert atmosphere; | 1.1 Step 1. N' - [4-(benzyloxy)cyclohexylidene] (tert-butoxy)carbohydrazide To a solution of 4-(benzyloxy)cyclohexan-l-one (5 g, 0.025 mol) in methanol (25 mL) was added (tert-butoxy)carbohydrazide (3.2 g, 0.025 mol). The resulting solution was stirred for 1 h at rt. The resulting mixture was concentrated to minimum volume, filtered and dried under vacuum to afford N-4-(benzyloxy)cyclohexylidene](tert-butoxy)carbohydrazide as a yellow solid (3 g, 35%). 319 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chlorotriisopropylsilane; trimethylsilyl trifluoromethanesulfonate at -40 - -10℃; for 2h; Inert atmosphere; | 71.1; 72.1 Step 1: Methyl (2R,3S,5R)-2-(((4-(benzyloxy)cyclohexyl)oxy)methyl)-3-(N-(4-methoxybenzyl)methylsulfonamido)-5-methylpyrrolidine-1-carboxylate (71-1) A solution of methyl (2R,3S,5R)-3-(N-(4-methoxybenzyl)methylsulfonamido)-5-methyl-2-(((triethylsilyl)oxy)methyl)pyrrolidine-1-carboxylate (S) 3.0 g (5.99 mmol), 4-(benzyloxy)cyclohexan-1-one (1.591 g, 7.79 mmol) and TRIISOPROPYLSILANE (2.455 ml, 11.98 mmol) at -40° C. under N2 was treated with TRIMETHYLSILYL TRIFLUORO-METHANE-SULFONATE (1.084 ml, 5.99 mmol) using a Hamilton syringe and needle and the mixture stirred at -40° C. for 2 h (temp rise to -10 C). The reaction was quenched with Sat. Aq NaHCO3 and diluted with EtOAc. After warming to rt the layers were separated and the aq layer washed EtOAc. The combined organics was dried (MgSO4), filtered and concentrated under reduced pressure to afford the crude. The crude was purified by silica gel chromatography, on the Combiflash NextGen 300+ with ELSD on an 80 g column, eluting with a gradient of ethyl acetate:ethanol (3:1)/hexanes-0:100 to 30:70 to afford the title compound (cis/trans). MS: m/z=575.4 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chlorotriisopropylsilane; trimethylsilyl trifluoromethanesulfonate In dichloromethane; acetonitrile at -30 - 0℃; for 4h; Inert atmosphere; | 1; 35.3; 36.3 Step 3: methyl (2R,3S,5R)-2-(((4-(benzyloxy)cyclohexyl)oxy)methyl)-3-((N,N-dimethyl-sulfamoyl)(4-methoxybenzyl)amino)-5-methylpyrrolidine-1-carboxylate (36-3) To a solution of methyl (2R,3S,5R)-3-((N,N-dimethylsulfamoyl)(4-methoxybenzyl)amino)-5-methyl-2-(((triethyl silyl)oxy)methyl)pyrrolidine-1-carboxylate (36-2) (3.32 g, 6.27 mmol) in Acetonitrile (48 ml) at 0° C. was added 4-(benzyloxy)cyclohexan-1-one (1.92 g, 9.40 mmol) followed by triisopropylsilane (2.57 ml, 12.53 mmol) under N2. Then the reaction mixture was cooled to -30° C., trimethylsilyl trifluoromethanesulfonate (1.134 ml, 6.27 mmol) was added. It was continued to stir at -30° C. for 4 hrs. LC-MS showed almost completion. The reaction mixture was quenched with sat. aq. NaHCO3. The reaction mixture was extracted by 2 portions of 10 ml of DCM. The combined organic phase was collected and concentrated to leave yellow oil. The residue was purified by ISCO (Loaded onto a 80 g column, eluent with 0˜55% EtOAc/hexane, the peak was collected at 50% EtOAc/hexane) to give the title compound methyl (2R,3S,5R)-2-(((4-(benzyloxy)cyclohexyl)oxy)methyl)-3-((N,N-dimethylsulfamoyl)(4-methoxybenzyl)amino)-5-methylpyrrolidine-1-carboxylate (36-3). LC-MS 604 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | In tetrahydrofuran at 20℃; for 16h; Cooling; Inert atmosphere; | 1 step 1; 4-(benzyloxy)-1-methylcyclohexan-1-ol To a stirred solution of 4-(benzyloxy)cyclohexan-l-one (2.50 g, 12.24 mmol) in THF (25.00 mL) was added 1 M CTHMgBr in THF (3.18 mL, 3.18 mmol) dropwise at -70 °C under nitrogen atmosphere. The reaction mixture was stirred for 16 h at room temperature under nitrogen atmosphere. The resulting mixture was quenched with aqueous MLCl (sat., 100 ml) at 0 °C. The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers was washed with brine (50 mL), dried over anhydrous NaiSCL. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with EA in PE (50%). The fractions contained desired product were combined and concentrated to afford 4-(benzyloxy)-l-methylcyclohexan-l-ol (1.05 g, 39%) as light yellow oil. H-NMR (400 MHz, CDCh) d 7.40-7.33 (m, 5H), 4.59-4.52 (m, 2H), 3.61-3.55 (m, 1H), 1.90-1.69 (m, 6H), 1.50- 1.40 (m, 2H), 1.29-1.25 (m, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-bromo-4-(trifluoromethoxy)benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: 4-(benzyloxy)cyclohexanone In tetrahydrofuran; hexane at -78℃; for 1.5h; | 272 Synthesis of 4-(4-(tetrahydro-2H-pyran-4-yl)phenoxy)-1H-1,2,3-triazole-5- carboxylic acid 2,2,2-trifluoroacetate (263) General procedure: To a solution of 1-(benzyloxy)-4-bromobenzene (263A) (1.3 g, 5 mmol) in anhydrous THF (20 mL) was dropped a solution of n-BuLi in n-hexane (2.5 M, 2.4 mL, 6 mmol) at -78 oC under nitrogen and stirred at -78 oC for 1 hour, followed by addition of dihydro-2H- pyran-4(3H)-one (263B) (0.56 mL, 6 mmol). The mixture was stirred at -78 oC for 1.5 hours, quenched with saturated NH4Cl solution (50 mL), and extracted with ethyl acetate (50 mL x 3). The combined organic layers was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, 20% to 100% v/v) to give Compound 263C. LC-MS (ESI) m/z: 267 [M-OH]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With (1,2-dimethoxyethane)dichloronickel(II); [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; tris[(2-pyridylmethyl)amine] In 2,2,2-trifluoroethanol at 25℃; for 16h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | Stage #1: 4-(benzyloxy)cyclohexanone With trimethylsilyl trifluoromethanesulfonate; triethylamine In dichloromethane at -5 - 0℃; for 3.25h; Inert atmosphere; Stage #2: With Selectfluor In acetonitrile at 25℃; for 3h; Inert atmosphere; | Step 1: rac-(2R,4R)-4-benzyloxy-2-fluoro-cyclohexanone To a mechanically stirred solution of 4-benzyloxycyclohexanone (500 g, 2.45 mol) and triethylamine (997 mL, 7.17 mol, 2.9 equiv.) in dichloromethane (DCM) (7 L) at -5°C under nitrogen was dropwise added a solution of trimethylsilyl trifluoromethanesulfonate (491 mL, 2.78 mol, 1.1 equiv.) in DCM (1.5 L) over 3 hours while maintaining the temperature below 0°C. The mixture was mechanically stirred for 15 minutes at 0°C and then a saturated auqueous NaHCO3 solution (10 L) was added. After stirring for 5 minutes the layers were separated. The aqueous layer was extracted with DCM (1 L). The combined organic layers were washed with brine (2.5 L), dried over sodium sulfate and concentrated under reduced pressure to give the corresponding trimethylsilyl enol ether (816.7 g) as a brown oil. To a solution of the resulting intermediate (816.7 g, 2.45 mol) in acetonitrile (7.5 L) was portionwise added Selectfluor (1101 g, 3.11 mol, 1.3 eq) in 1 hour while maintaining the temperature below 25°C with an ice-bath. The mixture was stirred for 2 hours allowing the temperature to warm up to room temperature. Diethylether (10 L) was added, and the precipitate was filtered through Celite and washed with diethylether (3 L). The filtrate was concentrated under reduced pressure to give 1198 g of a crude mixture of diastereomers as a brown oil. This mixture was separated by column chromatography on silica gel eluting with a gradient of 0.05% to 5% methanol in dichloromethane. The second eluting product was collected and concentrated under reduced pressure then taken into ethyl acetate (220 mL) followed by heptane (880 mL). After stirring for 45 minutes, the product was filtered, washed with heptane (100 mL) and dried under vacuum to give 110 g (20%) of rac-(2R,4R)-4-benzyloxy-2-fluoro-cyclohexanone as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-(benzyloxy)cyclohexanone With potassium <i>tert</i>-butylate In <i>tert</i>-butyl alcohol at 20℃; for 1h; Stage #2: methyl iodide In <i>tert</i>-butyl alcohol at 20℃; for 1h; | Step 3: To a solution of 4-(benzyloxy)cyclohexan-l-one (100 g, 489 mmol) in /-BuOH (1.0 L) was added potassium tert-butoxide (137 g, 1.22 mol). The resulting mixture was stirred at ambient temperature for 1 h. Iodomethane (145 g, 1.03 mol) was added dr op wise and the mixture was stirred at ambient temperature for 1 h. Then the mixture was quenched with saturated aqueous NH4CI (5.0 L) and extracted with ethyl acetate (3x). The combined organic layers were washed with brine (1.0 L) and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with a gradient of ethyl acetate : petroleum ether (1 : 100 to 5 : 100) to yield 4-(benzyloxy)-2,2-dimethylcyclohexan-l-one. MS: 233 (M + H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With hydroxyamino hydrochloride; anhydrous Sodium acetate In methanol; water monomer at 100℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: hydroxyamino hydrochloride; anhydrous Sodium acetate / water monomer; methanol / 2 h / 100 °C / Inert atmosphere 2: p-toluenesulfonyl chloride; pyridine; dmap / 72 h / 25 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: hydroxyamino hydrochloride; anhydrous Sodium acetate / water monomer; methanol / 2 h / 100 °C / Inert atmosphere 2: p-toluenesulfonyl chloride; pyridine; dmap / 72 h / 25 °C / Inert atmosphere 3: sodium hydride / tetrahydrofuran; mineral oil; N,N-dimethyl-formamide / 1 h / 0 - 25 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | Stage #1: 1-bromo-4-(pentafluoro-λ6-sulfanyl)benzene With n-butyllithium In tetrahydrofuran at -78℃; for 0.75h; Inert atmosphere; Stage #2: 4-(Phenylmethoxy)cyclohexanone In tetrahydrofuran at -78 - 25℃; for 16h; | 1.1 Step 1: Preparation of 4-(benzyloxy)-1-[4-(pentafluoro-λ6- sulfanyl)phenyl]cyclohexan-1-ol: Into a 250 mL 3-necked round-bottom flask, equipped with a magnetic stir bar and under nitrogen was added 1-bromo-4-(pentafluoro-λ6-sulfanyl)benzene (9.0 g, 31.8 mmol, 1.0 equiv) and THF (30 mL). The mixture was cooled to -78 °C in a dry ice/acetone bath and treated with drop-wise addition of n-BuLi (19 mL, 47.7 mmol, 1.5 equiv) over 15 minutes. After stirring at -78 °C for another 30 minutes, 4-(benzyloxy)cyclohexan-1-one (7.1 g, 35.0 mmol, 1.1 equiv) in THF (10 mL) was added drop-wise. The resulting mixture was maintained at -78 °C for 10 minutes before being warmed to room temperature and stirred at 25 °C for 16 h. The reaction was then quenched with saturated aqueous NH4Cl (20 mL) and extracted with ethyl acetate (3 × 10 mL). The combined organic layers were concentrated under reduced pressure. The crude product was purified by preparative-HPLC under the following conditions: Column, C18 silica gel; Mobile phase, water:MeCN (90:10), increasing to water:MeCN (40:60) within 20 min; Detector, UV 220 nm. The product containing fractions were combined, concentrated and dried under vacuum to afford the title product as a light yellow solid (1.5 g, 34% yield). |
Tags: 2987-06-6 synthesis path| 2987-06-6 SDS| 2987-06-6 COA| 2987-06-6 purity| 2987-06-6 application| 2987-06-6 NMR| 2987-06-6 COA| 2987-06-6 structure
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