Sulfuric Acid → Ethanedioic acid, 1,2-bis[(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl] ester, rel-

HRID 630574Notes

Reaction equation

HRID 630574 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].[CH:7]1([CH3:17])[CH2:12][CH2:11][CH:10]([CH:13]([CH3:15])[CH3:14])[CH:9]([OH:16])[CH2:8]1.OS(O)(=O)=O>N1C=CC=CC=1>[CH:13]([C@@H:10]1[CH2:11][CH2:12][C@@H:7]([CH3:17])[CH2:8][C@H:9]1[O:16][C:1](=[O:5])[C:2]([O:16][C@@H:9]1[CH2:8][C@H:7]([CH3:17])[CH2:12][CH2:11][C@H:10]1[CH:13]([CH3:15])[CH3:14])=[O:3])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 1254MentholHCID 65578Oxalyl chloride

Product 1

HCID 11383005Ethanedioic acid, 1,2-bis[(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl] ester, rel-

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Oxalyl chloride (12.1 g, 96.2 mmol) was added dropwise during 20 min to a stirred solution of (−)-menthol (30.0 g, 192.0 mmol) in pyridine (240 mL) at 0° C. The reaction mixture was allowed to warm up to room temperature overnight, then added to H2SO4 (50%, containing ice, 400 mL), extracted with ether (400 mL and 200 mL), treated again with H2SO4 (50%, containing ice, 400 mL), washed with a saturated solution of NaCl (200 mL) and a saturated solution of NaHCO3 (200 mL, 2×). The organic layer was dried (Na2SO4) and concentrated. Column chromatography (SiO2, heptane/diethyl ether 9:1) gave, after drying under vacuum (0.5 mbar, 1 h), 26.2 g (74%) of an oil.

Workup

  1. extractionextracted with ether (400 mL and 200 mL)
  2. additiontreated again with H2SO4 (50%, containing ice, 400 mL)
  3. washwashed with a saturated solution of NaCl (200 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated
  6. customColumn chromatography (SiO2, heptane/diethyl ether 9:1) gave
  7. dry with materialafter drying under vacuum (0.5 mbar, 1 h), 26.2 g (74%) of an oil

Sources & evidence

ORD record
ord-7db9cb3f8225412c90831048e5930ad8
Source dataset
uspto-grants-2016_04
Patent number
US09315763B2

Reaction notes

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