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Chemical Structure| 17429-02-6 Chemical Structure| 17429-02-6
Chemical Structure| 17429-02-6

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Synonyms: 4-Hydroxy-4-methylcyclohexanone

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Product Details of 4-Hydroxy-4-methylcyclohexanone

CAS No. :17429-02-6
Formula : C7H12O2
M.W : 128.17
SMILES Code : O=C1CCC(C)(O)CC1
Synonyms :
4-Hydroxy-4-methylcyclohexanone
MDL No. :MFCD13659404
InChI Key :MACNVPBGMHPCML-UHFFFAOYSA-N
Pubchem ID :28539

Safety of 4-Hydroxy-4-methylcyclohexanone

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 4-Hydroxy-4-methylcyclohexanone

* 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.

  • Downstream synthetic route of [ 17429-02-6 ]

[ 17429-02-6 ] Synthesis Path-Downstream   1~35

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YieldReaction ConditionsOperation in experiment
92% With hydrogenchloride; water; In tetrahydrofuran; at 20℃; for 6h; Step 2: Synthesis of 4-hydroxy-4-methylcyclohexanone [567] 8-Methyl-1,4-dioxaspiro[4.5]decane-8-ol (650 mg, 3.77 mmol) was dissolved in THF (10 ml), followed by addition of 1N aqueous HCl solution (5 ml), and then the resulting mixture was stirred at room temperature for 6 hours. The resulting reaction liquid was concentrated under reduced pressure, and then extracted with 10% MeOH/MC (20 ml x 5). The organic layer was dried over anhydrous sodium sulfate, followed by filtration and concentration, and then the residue thus obtained was subjected to MPLC (50% EtOAc/Hexanes), to obtain 443 mg of yellow oil (92%).
86.7% With hydrogenchloride; In tetrahydrofuran; water; at 20℃; Step 2: synthesis of 4-hydroxy-4-methylcyclohexanone To a solution of 8-methyl-1,4-dioxaspiro[4.5]decan-8-ol (6.1 g, 35.5 mmol) in THF (200 mL) was added 2 N HC1 (32 mL). The resulting mixture was stuffed at RT overnight, and then was basified to pH 8.0 by saturated K2C03 solution. The separated organic layer was concentrated invacuo and the residue was purified by column chromatography on silica gel (EA: PE= 3:20 to2:3) to afford the title compound as yellow oil (4.1 g, yield: 86.7%).
86% With pyridinium p-toluenesulfonate; In water; acetone; for 8h;Reflux; To a solution of 8-methyl-1,4-dioxaspiro[4.5]decan-8-ol (1 equiv) in a 2:1 mixture of acetone and water (0.38 M) was added pyridinium p-toluenesulfonate (0.2 equiv). The resulting mixture was refluxed for 8 h. After the reaction was complete, the reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography (0-30% ethyl acetate in petroleum ether) to afford the title compound (86% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d1) delta ppm 3.96-3.93 (m, 2H), 2.27-2.25 (m, 1H), 2.25-2.22 (m, 1H), 2.01-1.94 (m, 2H), 1.90-1.82 (m, 2H), 1.38 (s, 3H).
86.7% With hydrogenchloride; In tetrahydrofuran; water; at 20℃; Step 2: synthesis of 4-hydroxy-4-methylcyclohexanone To a solution of 8-methyl-1,4-dioxaspiro[4.5]decan-8-ol (6.1 g, 35.5 mmol) in THF (200 mL) was added 2 N HCl (32 mL). The resulting mixture was stirred at RT overnight, and then was basified to pH 8.0 by saturated K2CO3 solution. The separated organic layer was concentrated in vacuo and the residue was purified by column chromatography on silica gel (EA:PE=3:20 to 2:3) to afford the title compound as yellow oil (4.1 g, yield: 86.7%).
86.7% With hydrogenchloride; In tetrahydrofuran; water; at 20℃; To a solution of 8-methyl-1,4-dioxaspiro[4.5]decan-8-ol (6.1 g, 35.5 mmol) in THF (200 mL) was added 2 N HCl (32 mL). The resulting mixture was stirred at RT overnight, and then was basified to pH 8.0 by saturated K2CO3 solution. The separated organic layer was concentrated in vacuo and the residue was purified by column chromatography on silica gel (EA:PE=3:20 to 2:3) to afford the title compound as yellow oil (4.1 g, yield: 86.7%).
84% With hydrogenchloride; water; In acetone; at 40℃; for 14h;Inert atmosphere; Step 2. Preparation of 4-hydroxy-4-methylcyclohexanone To a solution of 8-methyl-l,4-dioxaspiro[4.5]decan-8-ol (5.26 g, 30.5 mmol) in acetone (40 mL) and water (60 mL) at room temperature was added 4 M HC1 (22.91 mL, 92 mmol). The reaction mixture was heated at 40 C for 14 h. The mixture was cooled to room temperature and was neutralized by the addition of solid sodium carbonate. The acetone was removed on the rotovapor and the aqueous layer was extracted with ethyl acetate (7 x 150 mL). The combined organic layers were dried over MgS04, filtered, and concentrated. The product was purified by column chromatography on silica gel (70% ethyl acetate in hexanes) to afford 4-hydroxy-4-methylcyclohexanone (3.27 g, 25.5 mmol, 84% yield) as a white solid: 1H NMR (400MHz, CHLOROFORM-d) delta 2.80 - 2.68 (m, 2H), 2.30 - 2.20 (m, 2H), 2.04 - 1.94 (m, 2H), 1.92 - 1.80 (m, 2H), 1.56 (s, 1H), 1.39 (s, 3H); 13C MR (100MHz, CHLOROFORM-d) delta 21 1.55, 68.14, 38.40, 36.80, 29.51.
82% With hydrogenchloride; In tetrahydrofuran; water; at 20℃; for 16h; Compound 1A (5.1 g, 29.6 mmol) was dissolved in THF (100 mL), followed by addition of 1N aqueous HCl (44.4 mL, 44.4 mmol) at room temperature. The resulting mixture was stirred at room temperature for 16 h. The resulting reaction liquid was concentrated under reduced pressure and then extracted with 10% MeOH/DCM (2*200 mL). The combined organic layer were washed with brine (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford 1B (yellow liquid, 3.1 g, 24.19 mmol, 82% yield) which was used in next step without further purification. 1H NMR (300 MHz, CDCl3) delta 2.81-2.65 (m, 2H), 2.32-2.15 (m, 2H), 2.01-1.75 (m, 4H), 1.36 (s, 3H).
With hydrogenchloride; water; at 20℃; for 48h; A mixture of 8-methyl-1 ,4-dioxa-spiro[4.5]decan-8-o. (Step BB.7, 9.35 g, 54.3 mmol), water (400 ml) and hydrochloric acid (0.3 ml) was stirred at room temperature for 48 hours and then extracted 3X with ethyl acetate. The combined organic layers were dried over magnesium sulphate and evaporated at 40 C under a vacuum of 170 mbar to give the title compound as a pale yellow oil. 1H NMR (400 MHz, CDCI3) delta ppm 1.29-1.40 (m, 1 H), 1.58 (s, 1 H), 1.85 (td, 1 H), 1.97 (qd, 1 H), 2.24 (d, J = 14.8 Hz, 1 H), 2.72 (td, J = 13.7, 6.3 Hz, 1 H).
With hydrogenchloride; In tetrahydrofuran; water; at 20℃; To a solution of 8-methyl-1 ,4-dioxaspiro[4.5]decan-8-ol (1 1 .78 g, 68.4 mmol) in THF (50 mL) was added aqueous HCI (1 M, 205 mL, 205.2 mmol). The reaction mixture was allowed to stir overnight at room temperature. Then, a saturated solution of Na2C03 was added and the mixture extracted with DCM. The combined organic extracts were dried over Na2S04, filtered and concentrated under reduced pressure to afford crude 4-hydroxy-4-methyl-cyclohexanone (6.18 g, 48.2 mmol, 71 % yield). NMR (400 MHz, CDCI3, delta): 2.70-2.61 (m, 2H), 2.21 -2.14 (m, 2H), 1 .94-1 .87 (m, 2H), 1 .83-1 .75 (m, 2H), 1 .31 (s, 3H), 1 .23 (s, 1 H).
With hydrogenchloride; In tetrahydrofuran; at 0 - 20℃; for 14h; General procedure: Hydrochloric acid (1 M, 3.0 eq.) was added to a suspension of 1 ,3-dioxolane derivative (1.0 eq.) in THF (1 M), cooled at 0 C. The reaction mixture was allowed to return to RT and stirred for 14 h. The mixture was then carefully basified with a saturated solution of sodium carbonate and the aqueous layer was extracted with DCM (x 3). The combined organic extracts were filtered over a phase separator and concentrated under reduced pressure to afford crude carbonyl; Following general procedure J, 8-methyl-i ,4-dioxaspiro[4.5]decan-8-ol (2.50 mmol) in THF (2.5 mL)afforded the titled compound crude (2.50 mmol) as a brown oil. 1H NMR (400 MHz, CDCI3, ): 2.71 -2.59(m, 2H), 2.23-2.12 (m, 2H), 1.96-i .86 (m, 2H), 1.85-i .73 (m, 2H), 1.31 (5, 3H), 1.23 (5, 1H)
With hydrogenchloride; In water; at 70℃; for 2.5h; To a stirred solution of 0.05 N HCl (1800 mL) was added 8-methyl-1,4- dioxaspiro [4.5] decan-8-ol (140.0 g, 0.814 mol). The mixture was stirred at 70 C for 2.5 hours. The resulting mixture was cooled to room temperature and added NaCl solid to saturation, then extracted with EtOAc (5 700 mL). The combined organic phase was dried over Na 2SO 4 and concentrated to give the 4-hydroxy-4-methylcyclohexan-1-one (105.0 g, crude) as a yellow oil.

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  • (2S,4R)-4-Hydroxy-2,4-dimethyl-cyclohexanone [ No CAS ]
  • (2R,4R)-4-Hydroxy-2,4-dimethyl-cyclohexanone [ No CAS ]
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YieldReaction ConditionsOperation in experiment
With methanol; sodium tetrahydroborate; at 20℃; To a cooled (0 C.) solution of <strong>[17429-02-6]4-hydroxy-4-methylcyclohexanone</strong> (1 equiv) in MeOH (0.5 M) was added sodium borohydride (2 equiv). The resulting mixture was stirred at room temperature overnight. After the reaction was complete, the resulting mixture was quenched with water and extracted with ethyl acetate. The organic layers were combined, washed with brine (20 mL), dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel flash column chromatography (0-10% DCM in MeOH) to afford the title compound as a white solid (87% yield, cis/trans mixture). 1H NMR (300 MHz, DMSO-d6) delta ppm 4.34-4.32 (d, J=4.5 Hz, 1H), 4.29-4.27 (d, J=3.6 Hz, 0.45H), 4.12-4.06 (m, 0.47H), 4.00 (s, 0.39H), 3.97 (s, 1H), 3.82 (s, 0.48H), 3.55-3.50 (m, 0.47H), 3.20-3.17 (d, J=7.5 Hz, 1H), 1.76-1.62 (m, 1H), 1.60-1.40 (m, 8H), 1.35-1.20 (m, 4H), 1.07 (s, 1.5H), 1.05 (s, 3H).
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  • 4-(methoxymethylene)-1-methylcyclohexanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Preparation Example 267 To a suspension of (methoxymethyl)(triphenyl)phosphonium chloride (164.57 g) which had been cooled in a dry ice-acetone bath in THF (500 ml) was added dropwise a solution of n-butyllithium in hexane (concentration 1.65 M, 281.3 ml) at -55C or lower under a nitrogen air flow. Then, the mixed reaction liquid was warmed, followed by stirring at room temperature for 1 hour. After stirring, the mixed reaction liquid was cooled under ice, and a solution of <strong>[17429-02-6]4-hydroxy-4-methylcyclohexanone</strong> (20.51 g) in THF (205 ml) was added dropwise thereto. After dropwise addition, the mixed reaction liquid was warmed to room temperature, followed by stirring for 15 hours. To the mixed reaction liquid were sequentially added water and EtOAc, followed by stirring, and then the organic layer was collected by separation. The aqueous layer was further extracted with EtOAc, and the organic layer was combined, washed with saturated brine, and dried over anhydrous sodium sulfate. After the desiccant was removed, the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (hexane-EtOAc) to obtain 4-(methoxymethylene)-1-methylcyclohexanol (21.37 g).
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  • 9-methyl-3-(1-phenylvinyl)-1,2,5-trioxaspiro[5.5]undec-9-ol [ No CAS ]
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  • (+)-dihydro-4-(2-hydroxyethyl)-4-methyl-2(3H)-furanone [ No CAS ]
  • (-)-dihydro-4-(2-hydroxyethyl)-4-methyl-2(3H)-furanone [ No CAS ]
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  • (-)-dihydro-4-(2-hydroxyethyl)-4-methyl-2(3H)-furanone [ No CAS ]
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  • (S)-5-(2-Hydroxy-ethyl)-5-methyl-dihydro-furan-2-one [ No CAS ]
  • [ 127718-14-3 ]
 

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