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CAS No. : | 695-06-7 | MDL No. : | MFCD00005401 |
Formula : | C6H10O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | JBFHTYHTHYHCDJ-UHFFFAOYSA-N |
M.W : | 114.14 | Pubchem ID : | 12756 |
Synonyms : |
γ-Caprolactone
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.83 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 30.13 |
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) : | -6.47 cm/s |
Log Po/w (iLOGP) : | 1.63 |
Log Po/w (XLOGP3) : | 0.74 |
Log Po/w (WLOGP) : | 1.1 |
Log Po/w (MLOGP) : | 0.88 |
Log Po/w (SILICOS-IT) : | 1.58 |
Consensus Log Po/w : | 1.19 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.95 |
Solubility : | 12.9 mg/ml ; 0.113 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.87 |
Solubility : | 15.3 mg/ml ; 0.134 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.12 |
Solubility : | 8.6 mg/ml ; 0.0753 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.81 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P264-P280-P305+P351+P338-P337+P313 | UN#: | N/A |
Hazard Statements: | H319 | 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 |
---|---|---|
87% | With ammonia at 20℃; for 240h; | |
With ethanol; ammonia at 100℃; | ||
With ammonia; water durch Schuetteln; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide und Erwaermen des Reaktionsgemisches; nicht rein erhalten; | ||
With hydrogen bromide for 18h; | ||
With hydrogen bromide; acetic acid at 20 - 70℃; for 7h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: hexan-4-olide With sodium hydroxide In ethanol Stage #2: With sodium hypochlorite In aq. phosphate buffer at 20℃; for 20h; | |
72% | With tetraethylammonium bromide In N,N-dimethyl-formamide at 20℃; | |
With sodium hydroxide; bromine; magnesium sulfate |
Multi-step reaction with 2 steps 1: NaOH / ethanol 2: NaOCl / aq. phosphate buffer / 20 h / 20 °C / pH 6.6 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With PPA at 100℃; | ||
13 EXAMPLE 13 EXAMPLE 13 By following the same procedure as in Example 3 except that 30 g of liquid γ-caprolactone was used as starting material in place of γ-methyl-ε-chlorocaproic acid in Example 3, 29.5 g of the product was obtained and rectified to afford 12.1 of 2-methyl-2-cyclopentenone and 7.3 g in all of 2-methyl-4-cyclopentenone and 2-cyclohexenone. | ||
14 EXAMPLE 14 EXAMPLE 14 By following the same procedure as in Example 2 except that 30 g of liquid γ-caprolactone was used as starting material in place of γ-methyl-ε-acetoxycaproic acid in Example 2, 29.0 g of the product was obtained and rectified to give 11.4 g of 2-methyl-2-cyclopentenone and 5.3 g in all of 2-methyl-4-cyclopentenone and 2-cyclohexenone. |
15 EXAMPLE 15 EXAMPLE 15 By following the same procedure as in Example 12 except that 30 g of liquid γ-caprolactone was used as starting material in place of γ-methyl-γ-chlorocapric acid in Example 12, 29.2 g of the product was obtained and rectified to afford 12.7 g of 2-methyl-2-cyclopentenone and 4.8 g in all of 2-methyl-4-cyclopentenone and 2-cyclohexenone. | ||
20 EXAMPLE 20 EXAMPLE 20 By following the same procedure as in Example 19 except that 30 g of liquid γ-caprolactone was used as starting material in place of ε-caprolactone in Example 19 and the heating temperature was a temperatue of 300°C, 29.6 g of the product was obtained and rectified to give 14.4 g of 2-methyl-2-cyclopentenone and 6.2 g in all of 2-methyl-4-cyclopentenone and 2-cyclohexenone. | ||
With phosphorus pentaoxide In phosphoric acid | C.1 COMPARATIVE EXAMPLE 1 COMPARATIVE EXAMPLE 1 In 120 ml of 85% phosphoric acid was dissolved 200 g of phosphorus pentoxide and 22.8 g of γ-caprolactone was added to the solution. The mixture was heated with stirring at a temperature of 100°C for 3 hours and then poured into water and extracted with ether. 9.8 g of the product thus obtained was subjected to quanatitative analysis by gas chromatography and the results showed that 0.25 g of 2-methyl-2-cyclopentenone was obtained and 0.22 g in all of 2-methyl-4-cyclopentenone and 2-cyclohexenone and 8.0 g of the unreacted γ-caprolactone were contained in it. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With trifluorormethanesulfonic acid In nitromethane for 3h; Heating; | |
With sulfuric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | In benzene alkalical hydrolysis; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With W(OTf)<SUB>6</SUB> at 180℃; for 10h; Schlenk technique; Ionic liquid; Inert atmosphere; Green chemistry; | |
With hydrogen iodide at 125℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With hydrogenchloride at 20℃; for 96h; | |
48% | With hydrogenchloride In methanol 1.) 0 deg C, 2.) 4 days, 35 deg C, sealed; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With pyridine In benzene at 140℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With hexafluoroantimonic acid at 0℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With lithium aluminium tetrahydride In diethyl ether at 0 - 20℃; for 16h; Inert atmosphere; | |
77% | With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; | |
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Ambient temperature; Yield given; |
With lithium aluminium tetrahydride In tetrahydrofuran | ||
With lithium aluminium tetrahydride | ||
With C21H24N4Ru(1+)*F6P(1-); potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 50℃; for 4h; | ||
With hydrogen In 1,4-dioxane at 170℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Yield given; | ||
Multi-step reaction with 2 steps 1: NaOH / ethanol / 2 h 2: (1S)-(+)-10-camphorsulfonic acid / various solvent(s) / in 99.5 percent EtOH | ||
Multi-step reaction with 2 steps 2: diethyl ether / 26 °C / porcine pancreatic lipase (PPL) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide In ethanol for 2h; Yield given; | ||
With sodium hydroxide In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With cethyltrimethylammonium permanganate In chloroform at 25℃; for 4h; | |
40% | With (bipyH2)-CrOCl5 In dichloromethane Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 40% 2: 50% | With chromium(V) | |
With potassium permanganate; water; copper(II) sulfate In dichloromethane 1.) reflux, 5 min, 2.) RT, 4 h; Yield given. Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With 1-Cyanonaphthalene In water; acetonitrile for 13.3333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 40% 2: 41% 3: 19% | With sodium persulfate; sodium chloride In water at 85 - 90℃; for 10h; | |
1: 40 % Chromat. 2: 41 % Chromat. 3: 19% | With sodium persulfate; sodium chloride In water at 85 - 90℃; for 10h; | |
1: 19 % Chromat. 2: 41 % Chromat. 3: 40 % Chromat. | With sodium persulfate; sodium chloride In water at 85 - 90℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In methanol; water at 0℃; for 1h; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With dodecacarbonyltetrarhodium(0); triphenylphosphine; isopropyl alcohol at 220℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With perchloric acid In dichloromethane for 8h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With disodium hydrogenphosphate In water pH=7.2; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 38% 2: 42% 3: 18% | With sodium persulfate; copper dichloride at 85 - 90℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sulfuric acid at 130℃; Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 60% 2: 22% | With sodium persulfate In water at 85 - 90℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 13 % Turnov. 2: 60 % Turnov. 3: 22 % Turnov. | With sodium persulfate; copper dichloride In water at 85 - 90℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With hydrogen iodide at 125℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With chloro-trimethyl-silane; water; sodium iodide In hexane for 18h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With calcium(II) bis(trifluoromethanesulfonyl)imide; tert-butylammonium hexafluorophosphate(V) at 80℃; for 2h; Sealed tube; | |
66% | With chloro-trimethyl-silane; water; sodium iodide In hexane for 44h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With Rhodococcus rhodochrous IFO 15564 at 30℃; phosphate buffer, pH 6; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ethanol; platinum Hydration; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper chromium at 180℃; | ||
With copper chromium at 180℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride In diethyl ether at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | hexan-4-olide; dimethyl lithiomethylphosphonate Stage #2: With lithium diisopropyl amide Stage #3: chloro-trimethyl-silane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; disodium hydrogenphosphate; porcine pancreating lipase In diethyl ether; hexane at 20℃; for 144h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With nickel; isopropyl alcohol for 0.25h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With 1,2-bis-(diphenylphosphino)ethane; methyl iodide at 80 - 90℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With methyl iodide at 80 - 90℃; for 12h; | |
30% | With methyl iodide at 80 - 90℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With Lawessons reagent; Hexamethyldisiloxane at 120℃; for 0.025h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: hexan-4-olide With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.333333h; Stage #2: trifluoroethyl trifluoroacetate In tetrahydrofuran at -78℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: acetic acid tert-butyl ester With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; Stage #2: hexan-4-olide In tetrahydrofuran; hexane at -78℃; Stage #3: tert-butyldimethylsilyl chloride With tert-butoxide In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: tert-butyl propionate With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; Stage #2: hexan-4-olide In tetrahydrofuran; hexane at -78℃; for 2h; Stage #3: tert-butyldimethylsilyl chloride With tert-butoxide In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Stage #1: ethyl acetate With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; Stage #2: hexan-4-olide In tetrahydrofuran; hexane at -78℃; Stage #3: tert-butyldimethylsilyl chloride With tert-butoxide In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: Benzyl propargyl ether With n-butyllithium In tetrahydrofuran at -78 - -30℃; Stage #2: hexan-4-olide With boron trifluoride diethyl etherate In tetrahydrofuran at -78 - 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: O-benzylhydoxylamine hydrochloride With trimethylaluminum In tetrahydrofuran; toluene at 0 - 20℃; for 0.833333h; Stage #2: hexan-4-olide In tetrahydrofuran; toluene at 0℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; lithium diisopropyl amide In tetrahydrofuran at -78℃; | |
Stage #1: hexan-4-olide With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #2: ethyl iodide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With diisobutylaluminium hydride In hexane; dichloromethane at -78℃; for 1h; | |
85% | With diisobutylaluminium hydride In tetrahydrofuran at -78℃; | |
52% | Stage #1: hexan-4-olide With diisobutylaluminium hydride In toluene at -63 - -61℃; for 1.5h; Inert atmosphere; Stage #2: With methanol In diethyl ether; toluene at 20℃; | 1.4 In argon atmosphere, γ-hexalactone (7) (11.4 g, 100 mmol) and toluene (200 mL) were added to a 500 mL flask and diisobutylaluminum hydride (DIBAL) (1.01 M in toluene, 109 mL, 0.110 mol) was added dropwise over 30 min at -63 to -61°C. After completion of the dropping, the reaction mixture was stirred for 1 h at the temperature as it was, followed by addition of methanol (20 mL), Celite and diethyl ether and stirring overnight at room temperature. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue (13.5 g) was distilled under reduced pressure (ca. 55°C / 0.5 kPa) to give the lactol (4) (6.00 g, 51.7 mmol, yield 52%, purity 93%). |
Stage #1: hexan-4-olide With diisobutylaluminium hydride In toluene at -63 - -61℃; for 1.5h; Inert atmosphere; Stage #2: With methanol In diethyl ether; toluene at 20℃; | 1.4 In argon atmosphere, γ-hexalactone (8) (11.4 g, 0.100 mol) and toluene (200 mL) were added to a 500 mL flask and diisobutylaluminum hydride (DIBAL) (1.01 M in toluene, 109 mL, 0.110 mol) was added dropwise over 30 min at -63 to -61°C. After completion of the dropping, the reaction mixture was stirred for 1 h at the temperature as it was, followed by addition of methanol (20 mL), Celite and diethyl ether, and stirring overnight at room temperature. The mixture was filtered, and the filtrate was evaporated under reduced pressure. The resulting residue (13.5 g) was distilled under reduced pressure (ca. 55°C / 0.5 kPa) to give the lactol (4) (6.00 g, 0.0517 mol, yield 52%, purity 93%). | |
Stage #1: hexan-4-olide With diisobutylaluminium hydride In hexane; dichloromethane at -75 - -70℃; for 4.5h; Stage #2: With water; ammonium chloride In hexane; dichloromethane Cooling with ice; | 7 2,4-Pentadienyltriphenylphosphonium bromide. Prepared as described in example 6. 5-Ethyltetrahydro-2-furanol. At -75° C., a solution of gamma-caprolactone (10.2 g, 98%, 87.6 mmol) in dichloromethane (200 ml) was treated within 60 min. with a 1M solution of diisobutylaluminium hydride in hexane (123 ml, 123 mmol). The resulting solution was stirred 3.5 h at -70° C. before being poured into an ice-cold solution of saturated aqueous NH4Cl (200 ml). The mixture was acidified with a 2M aqueous solution of hydrochloric acid (50 ml) and the organic phase was washed twice with water (100 ml). The aqueous phases were extracted with dichloromethane (100 ml) and the combined organic phases were dried (MgSO4), filtered, and concentrated to give crude 5-ethyltetrahydro-2-furanol (5.47 g, 53%) that was used as such in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: 68 percent / DMPU; LDA / tetrahydrofuran / -78 °C 2.1: LiAlH4 / tetrahydrofuran / 0 °C 2.2: DMAP; Et3N / CH2Cl2 / 20 °C 3.1: 98 percent / NaOH / methanol / 20 °C 4.1: 80 percent / imidazole / 20 °C 5.1: 66 percent / i-PrEt2N / Rh2(oct)4 / CH2Cl2 / 20 °C 6.1: 76 percent / tetrahydrofuran / 0 °C 7.1: 63 percent / TBAF / tetrahydrofuran / 20 °C 8.1: IBX / dimethylsulfoxide / 50 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: 68 percent / DMPU; LDA / tetrahydrofuran / -78 °C 2.1: LiAlH4 / tetrahydrofuran / 0 °C 2.2: DMAP; Et3N / CH2Cl2 / 20 °C 3.1: 98 percent / NaOH / methanol / 20 °C 4.1: 80 percent / imidazole / 20 °C 5.1: 66 percent / i-PrEt2N / Rh2(oct)4 / CH2Cl2 / 20 °C 6.1: 76 percent / tetrahydrofuran / 0 °C 7.1: 63 percent / TBAF / tetrahydrofuran / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: 68 percent / DMPU; LDA / tetrahydrofuran / -78 °C 2.1: LiAlH4 / tetrahydrofuran / 0 °C 2.2: DMAP; Et3N / CH2Cl2 / 20 °C 3.1: 98 percent / NaOH / methanol / 20 °C 4.1: 80 percent / imidazole / 20 °C 5.1: 66 percent / i-PrEt2N / Rh2(oct)4 / CH2Cl2 / 20 °C 6.1: 76 percent / tetrahydrofuran / 0 °C 7.1: 63 percent / TBAF / tetrahydrofuran / 20 °C 8.1: IBX / dimethylsulfoxide / 50 °C 9.1: n-BuLi / tetrahydrofuran; 2-methyl-propan-2-ol / -40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: 68 percent / DMPU; LDA / tetrahydrofuran / -78 °C 2.1: LiAlH4 / tetrahydrofuran / 0 °C 2.2: DMAP; Et3N / CH2Cl2 / 20 °C 3.1: 98 percent / NaOH / methanol / 20 °C 4.1: 80 percent / imidazole / 20 °C 5.1: 66 percent / i-PrEt2N / Rh2(oct)4 / CH2Cl2 / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: 68 percent / DMPU; LDA / tetrahydrofuran / -78 °C 2.1: LiAlH4 / tetrahydrofuran / 0 °C 2.2: DMAP; Et3N / CH2Cl2 / 20 °C 3.1: 98 percent / NaOH / methanol / 20 °C 4.1: 80 percent / imidazole / 20 °C 5.1: 66 percent / i-PrEt2N / Rh2(oct)4 / CH2Cl2 / 20 °C 6.1: 76 percent / tetrahydrofuran / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: nBuLi / tetrahydrofuran / -78 - -30 °C 1.2: 92 percent / BF3*OEt2 / tetrahydrofuran / 1 h / -78 - 20 °C 2.1: 76 percent / H2 / Pd/C / ethanol / 24 h / 20 °C / 760 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: LiN(SiMe3)2 / tetrahydrofuran / 0.33 h / -78 °C 1.2: tetrahydrofuran / 0.25 h / -78 °C 2.1: 3 Angstroem molecular sieves; Cs2CO3; o-nitrobenzenesulfonyl azide / Rh2(oct)4 / CH2Cl2 / 14 h / 0 - 23 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: LiN(SiMe3)2 / tetrahydrofuran / 0.33 h / -78 °C 1.2: tetrahydrofuran / 0.25 h / -78 °C 2.1: 3 Angstroem molecular sieves; Cs2CO3; o-nitrobenzenesulfonyl azide / Rh2(oct)4 / CH2Cl2 / 14 h / 0 - 23 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: NaH / diethyl ether / 3 h / 20 °C 2: NaBH4 / methanol / 1 h / 20 °C 3: pyridine 4: pyridine / 6 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: NaH / diethyl ether / 3 h / 20 °C 2: NaBH4 / methanol / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: NaH / diethyl ether / 3 h / 20 °C 2: NaBH4 / methanol / 1 h / 20 °C 3: pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) NaOH, 2.) glucose / 1.) MeOH, reflux, 2.) H2O, suspension of baker's yeast, 28 to 30 deg C, 25 h 2: conc. HCl / methanol; H2O / 1 h / 0 °C | ||
Multi-step reaction with 3 steps 1: NaBH4, Na2HPO4 / methanol / 5 h / Ambient temperature 2: aq. 10percent NaOH / methanol / 1 h / Ambient temperature 3: conc. HCl / methanol; H2O / 1 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: LiAlH4 / tetrahydrofuran / 2 h / Ambient temperature 2: pyridine / 2 h / 60 °C 3: pyridine / 18 h / Ambient temperature 4: PCC, AcOH / CH2Cl2 / 4 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: LiAlH4 / tetrahydrofuran / 2 h / Ambient temperature 2: pyridine / 2 h / 60 °C 3: pyridine / 18 h / Ambient temperature 4: PCC, AcOH / CH2Cl2 / 4 h / Ambient temperature 5: 1) KH / 1) monoglyme, 2 h, RT, 2) monoglyme, 6 h, RT 6: 5percent KOH in MeOH / 4 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 67 percent / pyridine / Co2(CO)8 / benzene / 6 h / 140 °C / 38000 Torr 2: 90 percent / HCl / H2O / 3.5 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 48 percent / HCl (gas) / methanol / 1.) 0 deg C, 2.) 4 days, 35 deg C, sealed 2: 59 percent / 1M diisobutylaluminum hydride/hexane / CH2Cl2 / 1 h / -78 °C | ||
Multi-step reaction with 2 steps 1: hydrogenchloride / 96 h / 20 °C 2: diisobutylaluminium hydride / dichloromethane / 1 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) MeLi / 1.) ether, ice bath, 5 min, 2.) ether, 3h 2: 5percent Rh/alumina, hydrogen / methanol / 760 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 48 percent / HCl (gas) / methanol / 1.) 0 deg C, 2.) 4 days, 35 deg C, sealed 2: 59 percent / 1M diisobutylaluminum hydride/hexane / CH2Cl2 / 1 h / -78 °C 3: tetrahydrofuran / 14 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 48 percent / HCl (gas) / methanol / 1.) 0 deg C, 2.) 4 days, 35 deg C, sealed 2: 59 percent / 1M diisobutylaluminum hydride/hexane / CH2Cl2 / 1 h / -78 °C 3: 1.) THF, 14 h, 20 deg C, 2.) 96 h, 60 deg C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 48 percent / HCl (gas) / methanol / 1.) 0 deg C, 2.) 4 days, 35 deg C, sealed 2: 59 percent / 1M diisobutylaluminum hydride/hexane / CH2Cl2 / 1 h / -78 °C 3: tetrahydrofuran / 14 h / 20 °C | ||
Multi-step reaction with 4 steps 1: 48 percent / HCl (gas) / methanol / 1.) 0 deg C, 2.) 4 days, 35 deg C, sealed 2: 59 percent / 1M diisobutylaluminum hydride/hexane / CH2Cl2 / 1 h / -78 °C 3: 1.) THF, 14 h, 20 deg C, 2.) 96 h, 60 deg C 4: 98 percent / (C2H5)3N / methanol / 24 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 1.) CH3Li / 1.) ether, 5 min, 2.) RT, 2 h 2: H2 / 5percent Rh/Al2O3 / methanol / 760 Torr 3: 3 M aq. HCl / 48 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.) CH3Li / 1.) ether, 5 min, 2.) RT, 2 h 2: H2 / 5percent Rh/Al2O3 / methanol / 760 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: NaOH / ethanol / 2 h 2: (1S)-(+)-10-camphorsulfonic acid / various solvent(s) / in 99.5 percent EtOH | ||
Multi-step reaction with 2 steps 1: O.1M Na2HPO4 / pig pancreatic lipase (PPL) / H2O / pH=7.2 2: HCl | ||
Multi-step reaction with 2 steps 2: diethyl ether / 26 °C / porcine pancreatic lipase (PPL) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.8% | In neat (no solvent) at 80 - 85℃; for 16h; Heating; Large scale; | |
In ethyl acetate | 1 4-Hydroxyhexanoic acid 4-methoxybenzylamide (2.0.0) EXAMPLE 1 4-Hydroxyhexanoic acid 4-methoxybenzylamide (2.0.0) Gamma-caprolactone (28.745 Kg, 251.8 moles) and 4-methoxybenzylamine (38.0 Kg, 277 moles) were placed in a 100 gallon glass lined tank. The solution was heated to 80-85° C. and held at that temperature for 16 hours. TLC on silica gel plates showed the reaction was complete. The TLC system comprised: ethyl acetate with detection at 254 nm. Ethyl acetate (18 gal, 68 L) was slowly charged to the reaction pot after cooling to 60° C. Hexanes (a total of 18 gal, 68 L) were added until a haze was achieved. After 1/2 hour, to allow crystallization to start, the remainder of the hexanes was added. The slurry was cooled to 25° C. and granulated for 3 hours. The solid was collected by filtration and washed with a 1:1 mixture of ethyl acetate and hexanes. The wet cake was vacuum dried with no additional heat to produce 46.05 Kg (72.8%) of the desired amide; mp 81-82° C. 1HMR (CDCl3, 300 MHz) 67.18 (d, 2), 6.84 (d, 2), 6.27 (bs, 1), 4.32 (d, 2), 3.79 (s,3), 3.50 (m, 1), 3.19 (bs, 1), 2.35 (t, 2), 1.85 (m, 1), 1.67 (m, 1), 1.49 (m, 2), 0.92 (t, 3). Anal. Calcd. for Cl4H21NO3: C, 66.91; H, 8.42; N, 5.57. Found: C, 67.26; H, 8.71; N, 5.55. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetylperoxyborate In water at 50℃; for 2h; | 15 The procedure of Example 6 was repeated but using cyclohexanone (2.65g), instead of the styrene, and using MnAlPO-5 (0.25g) as catalyst. The reaction temperature employed was 50°C and the reaction time was 2 hours.Conversion was 31.5% and the selectivity for γ-caprolactone was 99.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: hexan-4-olide With phosphorus tribromide at 20℃; for 0.166667h; Stage #2: With bromine at 100℃; for 2h; | 3 90% Phosphorus tribromide (2 g, 0.07 mol, manufactured by Wako Pure Chemical Industries, Ltd.) was added to 4-ethyl-4-butyrolactone (46 g, 0.4 mol, manufactured by ALDRICH) at room temperature, followed by stirring for 10 minutes. The reaction liquid was heated to 1000C, and bromine(64 g, 0.4 mol, manufactured by JUNSEI CHEMICAL CO., LTD.) was added dropwise over a period of 1 hour using a dropping funnel.After the completion of the dropwise addition, the reaction liquid was stirred for 1 hour at 1000C. After the reaction, the reaction liquid was cooled to room temperature, and water (100 g) was gradually added followed by stirring for 10 minutes. Subsequently, 200 g of ethyl acetate was added to perform extraction. The aqueous phase obtained by separating the organic phase was subjected to re-extraction with ethyl acetate (100 ml) .The organicphases thus extractedwere combined anddried over anhydrous sodium sulfate (manufacturedby JUNSEI CHEMICAL CO., LTD.) . The sodium sulfate was filtered out, and the organic phase was concentrated and distilled under reduced EPO pressure to give 2-bromo-4-ethyl-4-butyrolactone (50 g, bp:104°C/0.4 kPa, yield: 65% by mass) . |
65% | With bromine; phosphorus tribromide at 100℃; for 2h; | 3.1 (1) Production of 2-bromo-4-ethyl-4-butyrolactone;To46g (0.4 mol) of 4-ethyl-4-butyrolactone (manufactured by SIGMA-ALDRICH Corporation), 2 g (0.07 mol) of 90% phosphorus tribromide (manufactured by Wako Pure Chemical Industries Co., Ltd.) were added at room temperature and the resultant mixture was stirred for 10 minutes. The reaction solution was heatedup to 100°C, and 64 g (0.4 mol) of bromine (manufactured by JUNSEI CHEMICAL Co., Ltd.) were added dropwise thereinto through adropping funnel over one hour. After the completion of thedropwise addition, the reaction solution was stirred at 1000C for one hour.[0080]The reaction solution after the reaction was cooled to roomtemperature, and 100 g of water were gradually added thereto and the resultant mixture was stirred for 10 minutes. Further,the mixture was extracted by adding 200 g of ethyl acetate thereto. The aqueous phase obtained by separating the organic phase wasreextracted with 90 g of ethyl acetate. [0081]These extracted organic phases were combined and theresultant organic phase was dried by anhydrous sodium sulfate (manufactured by JUNSEI CHEMICAL Co. , Ltd. ) . The organic phase from which the sodium sulfate was filtered off was concentrated and distilled under a reduced pressure to give 50 g of 2-bromo-4-ethyl-4-butyrolactone (having a boiling point of104°C/0.4 kPa; with a yield of 65%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With Zn4(OCOCF3)6O In chlorobenzene for 36h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | Stage #1: methyllithium With copper(l) iodide In diethyl ether at 0℃; for 0.25h; Inert atmosphere; Stage #2: 5-bromomethyl-γ-butyrolactone In diethyl ether at -70 - 0℃; for 5.5h; Inert atmosphere; Stage #3: With ammonium chloride In diethyl ether; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | Stage #1: methylmagnesium bromide With copper(l) iodide In tetrahydrofuran; diethyl ether at 0℃; for 0.5h; Inert atmosphere; Stage #2: methyl 3-(oxiran-2-yl)propanoate In tetrahydrofuran; diethyl ether at -30℃; for 2h; Inert atmosphere; Stage #3: With ammonium chloride In tetrahydrofuran; diethyl ether; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | Stage #1: methyllithium With copper(I) cyanide In tetrahydrofuran; diethyl ether at 0℃; for 0.5h; Inert atmosphere; Stage #2: methyl 3-(oxiran-2-yl)propanoate In tetrahydrofuran; diethyl ether at -30℃; for 2h; Inert atmosphere; Stage #3: With ammonium chloride In tetrahydrofuran; diethyl ether; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With W(OTf)<SUB>6</SUB> at 180℃; for 10h; Schlenk technique; Ionic liquid; Inert atmosphere; Green chemistry; | |
With silica-alumina In water at 374.84℃; Flow conditions; | ||
99 %Chromat. | With W(OTf)6 at 150℃; for 10h; Green chemistry; | 1 Example 1 6-caprolactone was added to the reaction vessel,Further, 2 mol% of W (OTf) 6 based on 6-caprolactone was added,The temperature was raised to 150 ° C with stirring at a rate of 100 r / min,In solvent-free conditions rearrangement reaction 10h,Insulation rearrangement reaction kept stirring,After cooling to room temperature, the reaction solution was obtained,Then vacuum distillation to give γ-caprolactone.Sample dilution,The yield of γ-caprolactone was determined to be 99% by gas chromatography (GC)Purity is 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With isopropylmagnesium chloride In tetrahydrofuran at -20 - -15℃; for 0.333333h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium methylate In toluene at 50℃; for 70h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water at 374.84℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: neat (no solvent) / 16 h / 80 - 85 °C / Heating; Large scale 2.1: sodium tetrahydroborate / tetrahydrofuran / 0.5 h / 20 - 25 °C / Inert atmosphere; Large scale 2.2: 17 h / 0 - 66 °C / Inert atmosphere; Reflux; Large scale 3.1: ethyl acetate / 0 - 25 °C / Inert atmosphere; Large scale 4.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite; potassium bromide / dichloromethane; water / 0 - 15 °C / Large scale 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 - 25 °C / Large scale 6.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / Large scale 6.2: 16.5 h / 20 - 25 °C / Large scale 7.1: tetrahydrofuran / 88 °C / Inert atmosphere; Large scale 8.1: trifluoroacetic acid; methanesulfonic acid / 2 h / 50 - 70 °C / Large scale 9.1: dichloromethane / 21.66 h / 18 - 22 °C / Large scale 10.1: butan-1-ol / 48 h / 90 °C / Large scale | ||
Multi-step reaction with 10 steps 1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C 2: sodium tris(acetoxy)borohydride 3: triethylamine / dichloromethane 4: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / dichloromethane 5: sodium ethanolate / ethanol 6: dichloromethane 7: 120 °C 8: ammonium cerium (IV) nitrate; water / acetonitrile 9: dichloromethane / 21.66 h / 18 - 22 °C / Large scale 10: butan-1-ol / 48 h / 90 °C / Large scale | ||
Multi-step reaction with 11 steps 1.1: neat (no solvent) / 16 h / 80 - 85 °C / Heating; Large scale 2.1: sodium tetrahydroborate / tetrahydrofuran / 0.5 h / 20 - 25 °C / Inert atmosphere; Large scale 2.2: 17 h / 0 - 66 °C / Inert atmosphere; Reflux; Large scale 3.1: ethyl acetate / 0 - 25 °C / Inert atmosphere; Large scale 4.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite; potassium bromide / dichloromethane; water / 0 - 15 °C / Large scale 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 - 25 °C / Large scale 6.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / Large scale 6.2: 16.5 h / 20 - 25 °C / Large scale 7.1: tetrahydrofuran / 88 °C / Inert atmosphere; Large scale 8.1: trifluoroacetic acid; methanesulfonic acid / 2 h / 50 - 70 °C / Large scale 9.1: tetraphosphorus decasulfide / 1,4-dioxane 10.1: hydrazine; pyridine 11.1: pyridine / N,N-dimethyl-formamide / Reflux |
Multi-step reaction with 11 steps 1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C 2: sodium tris(acetoxy)borohydride 3: triethylamine / dichloromethane 4: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / dichloromethane 5: sodium ethanolate / ethanol 6: dichloromethane 7: 120 °C 8: ammonium cerium (IV) nitrate; water / acetonitrile 9: tetraphosphorus decasulfide / 1,4-dioxane 10: hydrazine; pyridine 11: pyridine / N,N-dimethyl-formamide / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: neat (no solvent) / 16 h / 80 - 85 °C / Heating; Large scale 2.1: sodium tetrahydroborate / tetrahydrofuran / 0.5 h / 20 - 25 °C / Inert atmosphere; Large scale 2.2: 17 h / 0 - 66 °C / Inert atmosphere; Reflux; Large scale 3.1: ethyl acetate / 0 - 25 °C / Inert atmosphere; Large scale 4.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite; potassium bromide / dichloromethane; water / 0 - 15 °C / Large scale 5.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / 20 - 25 °C / Large scale 6.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / Large scale 6.2: 16.5 h / 20 - 25 °C / Large scale 7.1: tetrahydrofuran / 88 °C / Inert atmosphere; Large scale 8.1: trifluoroacetic acid; methanesulfonic acid / 2 h / 50 - 70 °C / Large scale 9.1: tetraphosphorus decasulfide / 1,4-dioxane | ||
Multi-step reaction with 9 steps 1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C 2: sodium tris(acetoxy)borohydride 3: triethylamine / dichloromethane 4: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / dichloromethane 5: sodium ethanolate / ethanol 6: dichloromethane 7: 120 °C 8: ammonium cerium (IV) nitrate; water / acetonitrile 9: tetraphosphorus decasulfide / 1,4-dioxane |