Methanol → 2-((5-Methyl-2-(1-methylethyl)cyclohexyl)oxy)acetic acid

HRID 1110142Notes

Reaction equation

HRID 1110142 reaction equation
C(=[O:5])C(C)C.[CH3:6][CH:7]1[CH2:12][CH:11]([O:13][CH2:14][C:15](Cl)=[O:16])[CH:10]([CH:18]([CH3:20])[CH3:19])[CH2:9][CH2:8]1.CO>N1C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH3:6][CH:7]1[CH2:12][CH:11]([O:13][CH2:14][C:15]([OH:5])=[O:16])[CH:10]([CH:18]([CH3:20])[CH3:19])[CH2:9][CH2:8]1

Participants

7

Reactant 3

HCID 887MethanolHCID 6561IsobutyraldehydeHCID 556978HCID 556978, compound

Product 1

HCID 978142-((5-Methyl-2-(1-methylethyl)cyclohexyl)oxy)acetic acid

Reagents, catalysts & solvents 3

HCID 1049PyridineCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

1-L-menthoxyacetyloxy-2-methylpropene is prepared from isobutyraldehyde, L-menthoxyacetyl chloride, and pyridine catalyst. A 70 mL stainless steel high pressure reactor fitted with a Pyrex glass liner and magnetic stir bar is charged with THF (5 mL), (PPh3)2PdCl2 (0.05 mmol), CH3OH (0.5 mmol), and 1-L-menthoxyacetyloxy-2-methylpropene (0.5 mmol). The reactor is sealed, pressurized to 1000 psig with CO, and stirred for 24 hours at 100° C. The product mixture, isolated after removal of gas from the reactor vessel, contains a diastereomeric mixture of methyl 2-L-menthoxyacetyloxy-L-3-methylbutyrate and methyl 2-L-menthoxyacetyl-D-3-methylbutyrate. The diastereomers are separated by preparative gas chromatography using an SE-30 liquid phase column. Each diastereomer is hydrolyzed separately by treatment with 2N HCl (aq) for 2 hours at 100° C. to give pure L- and D-2-hydroxy-3-methylbutyric acid, methanol, and L-menthoxyacetic acid.

Workup

  1. customA 70 mL stainless steel high pressure reactor fitted with a Pyrex glass liner and magnetic stir bar
  2. customThe reactor is sealed
  3. customThe product mixture, isolated
  4. customafter removal of gas from the reactor vessel
  5. additiona diastereomeric mixture of methyl 2-L-menthoxyacetyloxy-L-3-methylbutyrate and methyl 2-L-menthoxyacetyl-D-3-methylbutyrate
  6. customThe diastereomers are separated by preparative gas chromatography
  7. waitEach diastereomer is hydrolyzed separately by treatment with 2N HCl (aq) for 2 hours at 100° C.

Sources & evidence

ORD record
ord-2bc686099aae4773bfef3b681c1196c0
Source dataset
uspto-grants-1994_06
Patent number
US05324856

Reaction notes

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