Structure of 14505-80-7
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| CAS No. : | 14505-80-7 |
| Formula : | C7H12O2 |
| M.W : | 128.17 |
| SMILES Code : | O=C1C[C@H](C)O[C@H](C)C1 |
| English Name : | cis-2,6-Dimethyldihydro-2H-pyran-4(3H)-one |
| MDL No. : | MFCD27944836 |
* 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 |
|---|---|---|
| 85% | With hydrogen In ethanol for 8h; | |
| 61% | With hydrogen In ethanol for 8h; | 58.A A mixture of ketone 58A {13.0 g), Pd/C (10%) (1.5 g) in EtOH (80 mL) was reacted in a hydrogenation vessel under 45 psi for 8 hours. Then the mixture was filtered through Celite and concentrated in vacuo. The residue was purified on a silica gel column (ISCO) with EtOAc in hexanes (0->25%) to provide 58B (8.0 g, 61% yield). |
| 29.1% | With Pd/C; hydrogen In methanol at 50℃; for 24h; | S4.1 Step 1. 2,6-dimethyltetrahydro-4H-pyran-4-one 2,6-dimethyltetrahydro-4H-pyran-4-one 2,6-dimethyl-4H-pyran-4-one (5 g, 40.3 mmol) was dissolved in dry MeOH (60 mL) and charged into a Buchi-steel autoclave with mechanical stirring. Pd/C (2.143 g, 2.014 mmol) was added and hydrogenation was accomplished at 50 °C and 25 bar H2 pressure for 24 h. The reaction mixture was filtered through a pad of Celite, and the filtrate was concentrated. The crude compound was purified via CombiFlash column chromatography (Redisep Rf 80 g silica gel column, 20% EtOAc in pet. ether as an eluent) to afford the title compound (1.5 g, 11.70 mmol, 29.1% yield) as a colorless oil. LCMS (ES): m/z = 129.2 [M+H]+ |
| 11% | With 10% Pd/C; hydrogen In ethanol; water at 20℃; for 16h; | |
| With methanol; palladium at 60℃; Hydrogenation; | ||
| With ethanol; nickel; palladium Hydrogenation.und Behandlung mit Chrom(VI)-oxid und wss. Schwefelsaeure; | ||
| Multi-step reaction with 2 steps 1: H2 / 10percent Pd/C / ethanol / 760 Torr / Ambient temperature 2: H2 / 10percent Pd/C / 760 Torr / Ambient temperature | ||
| With hydrogen In ethanol for 2h; | A [00307] Intermediate X13 was prepared from commercially available 2,6-dimethyl-g- pyrone (Aldrich Chemical Co., Milwaukee, Wisconsin, USA). A solution of the g-pyrone was dissolved in EtOH and hydrogenated (2 atm. H2) with 10% Pd/C over 2h. The catalyst was subsequently filtered off and the solution was concentrated in vacuo to yield crude X13 which was purified by column chromatography to yield pure compound X13. 1H-NMR (CDCl3, 500 MHz): 3.72 (m, 2H), 2.35 (m, 2H), 2.21 (dd, 2H), 1.32 (d, 6H) ppm. | |
| Stage #1: 2,6-dimethylpyrone With hydrogen In ethanol at 20℃; for 16h; Stage #2: With Dess-Martin periodane In dichloromethane at 20℃; for 16h; | 1 A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 mL) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperature. The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 mL) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 mL) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtO Ac/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (600 mg). GCMS: 128 [M]; Retention time = 4.25 mm. 1H NMR (400 MHz, DMSO-d6) δ [ppm]: 1.18 (d, J=6.26 Hz, 6 H) 2.11 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). | |
| Stage #1: 2,6-dimethylpyrone With hydrogen In ethanol at 20℃; for 16h; Stage #2: With Dess-Martin periodane In dichloromethane at 20℃; for 16h; | 1 A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 rriL) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperature. The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 mL) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 mL) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtO Ac/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran- 4(3H)-one (600 mg). GCMS: 128 [M]; Retention time = 4.25 mm. 1H NMR (400 MHz, DMSO-d6) δ [ppm]: 1.18 (d, J=6.26 Hz, 6 H) 2.11 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). | |
| Stage #1: 2,6-dimethylpyrone With hydrogen In ethanol at 20℃; for 16h; Stage #2: With Dess-Martin periodane In dichloromethane at 20℃; for 16h; | 1 A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 ml_) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperature. The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 ml_) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 ml_) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 ml_) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtOAc/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran- 4(3H)-one (600 mg). GCMS: 128 [M]; Rt = 4.25 min. H NMR (400 MHz, DMSO-d6) δ [ppm]: 1.18 (d, J=6.26 Hz, 6 H) 2.1 1 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). | |
| Stage #1: 2,6-dimethylpyrone With hydrogen In ethanol at 20℃; for 16h; Stage #2: With Dess-Martin periodane In dichloromethane at 20℃; for 16h; | Step 1. Preparation of (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-oneA solution of 2,6-dimethyl-4H-pyran-4-one (2g, 16.1 mmol) in 20ml ethanol was stirred over 10% Pd/C (0.2g) under hydrogen (15 psi) for 16 hours at ambient temperature. TLC showed two spots; one was desired product and second one was side product in a 1 : 1 ratio. GCMS M+ 128 for product, and M+ 130 for side product.Suspension was filtered off, and the filtrate was concentrated to remove solvent to give 2.3g crude product which contained -30% of the side product. The resulting oily residue was treated with 2.3g Dess-Martin periodinane in 15ml DCM at ambient temperature for 16 hours. GCMS showed oxidation was complete, desired product formation was confirmed by GCMS at M+ 128. ~3ml NaS2C03 was added to the suspension and the resulting mixture was stirred for 1 hour at ambient temperature, then 20ml saturated sodium bicarbonate solution was added to, and new mixture was stirred for another hour. The organic phase was separated, washed with water, brine, dried and filtered through celite. The filtrate was concentrated and resulting residue was purified by ISCO eluting with 10% ethyl acetate in heptane to yield 600 mg of the desired product. GCMS: M=128. HNMR: 1.5ppm (6H), 2.3ppm (4H), 3.75ppm (2H). | |
| Stage #1: 2,6-dimethylpyrone With hydrogen In ethanol at 20℃; for 16h; Stage #2: With Dess-Martin periodane In dichloromethane at 20℃; for 16h; | 1 A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 mL) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperatu The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 mL) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 mL) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtOAc/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (600 mg). GCMS: 128 [M]; Rt = 4.25 min. 1 H NMR (400 MHz, DMSO-d6) δ [ppm]: 1 .18 (d, J=6.26 Hz, 6 H) 2.1 1 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). | |
| Multi-step reaction with 2 steps 1: 10% Pd/C; hydrogen / ethanol / 17 h / 35 °C / 2585.81 Torr 2: sodium hydrogencarbonate; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium chlorite / dichloromethane; water / 6 h / 0 - 25 °C | ||
| Multi-step reaction with 2 steps 1: 10% Pd/C; hydrogen / ethanol / 17 h / 35 °C / 2585.81 Torr 2: sodium hydrogencarbonate; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium chlorite / dichloromethane; water / 6 h / 0 - 25 °C | ||
| Multi-step reaction with 2 steps 1: 10% Pd/C; hydrogen / ethanol / 17 h / 35 °C / 2585.81 Torr 2: TEMPO; sodium hydrogencarbonate; potassium bromide; sodium hypochlorite / water; dichloromethane / 6 h / 0 - 25 °C | ||
| With 10% Pd/C In tetrahydrofuran for 2h; | 31.A (2R,6S)-2,6-dimethyltetrahydro-4H-pyran-4-one 2,6-Dimethyl-4H-pyran-4-one (14 g) and tetrahydrofuran (140 mL) were added to 10% Pd/C, dry (2.8 g) in a 250 mL SS pressure bottle and the mixture was stirred for 2 hours at 50 psi. The mixture was filtered through a nylon membrane and concentrated. The crude product was chromatographed on silica gel with 5-50% ethyl acetate/hexanes to afford the title compound. | |
| Multi-step reaction with 2 steps 1: 10% Pd/C; hydrogen / methanol / 24 h / 50 °C / 2585.81 Torr 2: sodium hydrogencarbonate; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / dichloromethane; water / 25 h / 0 - 20 °C | ||
| Multi-step reaction with 2 steps 1: 10% Pd/C; hydrogen / ethanol / 17 h / 35 °C / 2585.81 Torr 2: sodium hydrogencarbonate; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / water; dichloromethane / 6 h / 0 - 25 °C | ||
| Stage #1: 2,6-dimethylpyrone With hydrogen In ethanol at 20℃; for 16h; Stage #2: With Dess-Martin periodane In dichloromethane at 20℃; for 16h; | 1 A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 mL) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperature. The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 mL) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 mL) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtOAc/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (600 mg). GCMS: 128 [M]; Retention time = 4.25 min. H NMR (400 MHz, DMSO-d6) δ [ppm]: 1.18 (d, J=6.26 Hz, 6 H) 2.11 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). | |
| Multi-step reaction with 2 steps 1: hydrogen; 10% Pd/C / ethanol / 35 °C 2: sodium acetate; pyridinium chlorochromate / dichloromethane / 2 h / 25 °C | ||
| 23 % | With 10% Pd/C; hydrogen In ethanol at 25℃; | 1 Step 1. Synthesis of cis-2,6-dimethyltetrahydro-4H-pyran-4-one To a solution of compound 2,6-dimethyl-4H-pyran-4-one (5.00 g, 40.3 mmol) in EtOH (50 mL) was added 10% Pd/C (500 mg) under N2 atmosphere. The mixture was degassed and purged with H2 for 3 times, then the mixture was hydrogenated (15 psi) at 25 °C for 16 hours. The reaction mixture was filtered and the solid was washed with EtOH (10 mL x2), the filtrate was concentrated. The residue was purified by silica gel column (PE/EtOAc = 3/1) to afford cis-2,6- dimethyltetrahydro-4H-pyran-4-one (1.20 g, yield: 23%) as yellow oil. |
| 23 % | With 10% Pd/C; hydrogen In ethanol at 25℃; | 1 Step 1. Synthesis of cis-2,6-dimethyltetrahydro-4H-pyran-4-one To a solution of compound 2,6-dimethyl-4H-pyran-4-one (5.00 g, 40.3 mmol) in EtOH (50 mL) was added 10% Pd/C (500 mg) under N2 atmosphere. The mixture was degassed and purged with H2 for 3 times, then the mixture was hydrogenated (15 psi) at 25 °C for 16 hours. The reaction mixture was filtered and the solid was washed with EtOH (10 mL x2), the filtrate was concentrated. The residue was purified by silica gel column (PE/EtOAc = 3/1) to afford cis-2,6- dimethyltetrahydro-4H-pyran-4-one (1.20 g, yield: 23%) as yellow oil. |
| Multi-step reaction with 2 steps 1: hydrogen; 10% Pd/C / ethanol / 16 h / 25 °C / 2327.23 Torr 2: sodium hydrogencarbonate; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / water; dichloromethane / 6 h / 0 - 20 °C | ||
| With 10% Pd/C; hydrogen In ethanol at 30℃; for 8h; | 3.1 Step 1: Synthesis of (2R, 6S)-2,6-dimethyltetrahydro-4H-pyran-4-one (3-1) Pd/C (10%, 10 g) was added to a solution of 2,6-dimethyl-4H-pyran-4-one (100 g, 0.810 mol) in ethanol (800 mL), and the mixture was stirred at 30°C under H2 (2 atm) for 8 h. The mixture was filtered through diatomaceous earth, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (PE/EA=3:1) to give a colorless oily crude compound 3-1 (53.0 g, 51.1%). |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With hydroxylamine | ||
| 16 g | With hydroxylamine hydrochloride; sodium acetate In ethanol at 60℃; for 3h; | 3.2 Step 2: Synthesis of (2R,6S)-2,6-dimethyltetrahydro-4H-pyran-4-one oxime (3-2) A suspension of compound 3-1 (15 g, 0.12 mol), hydroxylamine hydrochloride (8.1 g, 0.12 mol) and NaOAc (19.7 g, 0.24 mol) in ethanol (150 mL) was heated to 60 ° C and stirred for 3 h. After cooling to room temperature, the mixture was filtered, and the filtrate was concentrated in vacuo to obtain a residue. The residue was diluted in EtOAc and washed with brine. The separated organic layer was dried over anhydrous Na2SO4, filtered and concentrated to obtain a residue. The residue was purified by silica gel column chromatography (PE/EA=3:7) to obtain compound 3-2 as a white solid (16.0 g, 95.6%). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With hydrogen Ambient temperature; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 61% | With hydrogen In tetrahydrofuran for 24h; Ambient temperature; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 65% | With hydrogenchloride In tetrahydrofuran at 20℃; | |
| With hydrogenchloride In tetrahydrofuran at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 562 mg 2: 43 mg | With boron trifluoride diethyl etherate In tetrachloromethane at 20℃; for 12h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 55% | Stage #1: (2R,6S)-2,6-dimethyltetrahydro-4H-pyran-4-one With hydroxylamine hydrochloride In diethyl ether; water at 0℃; for 2h; Stage #2: at 110℃; for 0.25h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: 562 mg / BF3*OEt2 / CCl4 / 12 h / 20 °C 2: 78 percent / Na; liquid ammonia / 0.25 h / -78 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: 562 mg / BF3*OEt2 / CCl4 / 12 h / 20 °C 2.1: 78 percent / Na; liquid ammonia / 0.25 h / -78 °C 3.1: HCl / H2O / 2 h / Heating 3.2: SOCl2 / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 7 steps 1.1: 562 mg / BF3*OEt2 / CCl4 / 12 h / 20 °C 2.1: 78 percent / Na; liquid ammonia / 0.25 h / -78 °C 3.1: HCl / H2O / 2 h / Heating 3.2: SOCl2 / 20 °C 4.1: 335 mg / EDCI*HCl; HOBt; Et3N / CH2Cl2; dimethylformamide / 12 h / 20 °C 5.1: LiOH / H2O; tetrahydrofuran / 20 °C 6.1: TFA / CH2Cl2 / 20 °C 7.1: 98 mg / NaHCO3; DECP / dimethylformamide / 20 h / 20 °C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: 1.) mCPBA, 2.) LDA / 1.) CH2Cl2, 2.) THF, -78 deg C 2: O3 / CH2Cl2 / -78 - 20 °C 3: 100 percent / H2 / Raney Ni / ethanol / 50 °C / 38000 Torr |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: 93 percent / TsOH, MeOH / 40 h / Ambient temperature 2: 61 percent / hydrogen / 10 percent Pd/C / tetrahydrofuran / 24 h / 3750.3 Torr / Ambient temperature |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With β‐cyclodextrin at 24℃; for 24h; Resolution of racemate; neat (no solvent); optical yield given as %ee; enantioselective reaction; | ||
| With cyclopentadecanone monooxygenase-expressing Escherichia coli In 1,4-dioxane at 24℃; for 24h; Fermentation medium; Enzymatic reaction; optical yield given as %ee; enantioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86% | Stage #1: (2R,6S)-2,6-dimethyltetrahydro-4H-pyran-4-one; benzylamine With acetic acid In methanol for 1h; Stage #2: formaldehyd In methanol at 65℃; for 1h; Stage #3: With sodium hydroxide In methanol; water | 58.B A solution of 58B (2.56 g. 20.0 mmol), benzylamine (4.6 mL, 42.0 mmol) and acetic acid (2.28 mL, 40.0 mmot) in dry methanol (80 mL) was added over a period of 1 h to a suspension of coarse-grained paraformaldehyde (2.66 g, 88.4 mmol) in dry methanol (80 mL) at 65 °C. Another portion of paraformaldehyde (2.66 g, 88.4 mmol) was added and the mixture was stirred for 1 h at 65 °C. After cooling water (200 mL) and 1 N NaOH solution (40 mL) were added, and the aqueous phase was extracted with diethyl ether (3χ40() mL). The combined organic layers were dried over MgSO4 and the solvent was evaporated in vacuo. The residue was purified on a silica gel column (ISCO) with EtOAe in hexanes (0~>20%) to provide 58C (4.45 g, 86% yield). |