Tetrahydrofuran → HCID 178490597, compound

HRID 1508471Notes

Reaction equation

HRID 1508471 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[CH2:14][CH2:13][C@H:12]([CH:15]=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.CC(=CC)C.O.P([O-])(O)(O)=O.[Na+].Cl([O-])=O.[Na+].[Si](C=[N+]=[N-])(C)(C)C.[O:40]1CCC[CH2:41]1>O.CCOC(C)=O.CC(O)(C)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([O:40][CH3:41])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1

Participants

10

Reactant 6

HCID 8028TetrahydrofuranHCID 105532-Methyl-2-buteneHCID 167693TrimethylsilyldiazomethaneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium ChloriteHCID 178490595HCID 178490595, compound

Product 1

HCID 178490597HCID 178490597, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trans-4-(4-methoxyphenyl)cyclohexanecarbaldehyde (774 mg, 3.55 mmol) was dissolved in tetrahydrofuran (7.2 ml) and t-BuOH (18 ml) was added followed by 2-methyl-2-butene (7.2 ml, 68.0 mmol). To this solution was added sodium dihydrogen phosphate, hydrate (1072 mg, 7.80 mmol) as a solution in water (4.1 mL). Finally, sodium chlorite (882 mg, 7.80 mmol) was added as a solution in water (4.1 mL). The reaction was stirred at room temperature for 2 hours and then diluted with EtOAc (100 mL) and washed with water (25 mL) and brine (25 mL). The aqueous washes were combined, acidified with 1N HCl and extracted with EtOAc (50 mL). The two EtOAc extracts (before and after acidification) were combined, dried over Na2SO4, filtered, and concentrated. The residue was taken up in toluene (20 ml) and MeOH (3 ml). TMS-diazomethane (2.82 ml, 5.64 mmol) was added dropwise. Evolution of gas was observed, and a yellow color persisted. After 45 minutes, the reaction was quenched with HOAc, diluted with EtOAc (75 mL), and washed with saturated NaHCO3 and brine (20 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 0 to 40% EtOAc/hexanes afforded methyl trans-4-(4-methoxyphenyl)cyclohexanecarboxylate. 1H NMR (CDCl3, 500 MHz) δ 7.12 (d, J=8.7 Hz, 2H), 6.84 (d, J=8.5 Hz, 2H), 3.79 (s, 3H), 3.69 (s, 3H), 2.47 (m 1H), 2.35 (m, 1H), 1.92-2.12 (m, 4H), 1.53-1.63 (m, 2H), 1.40-1.49 (m, 2H).

Workup

  1. washwashed with water (25 mL) and brine (25 mL)
  2. extractionextracted with EtOAc (50 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. waitAfter 45 minutes
  7. customthe reaction was quenched with HOAc
  8. additiondiluted with EtOAc (75 mL)
  9. washwashed with saturated NaHCO3 and brine (20 mL each)
  10. dry with materialThe organic layer was dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification of the residue by flash chromatography on silica gel with 0 to 40% EtOAc/hexanes

Sources & evidence

ORD record
ord-7e5aee02905f495c8ca84f03a9929e67
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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