(-)-Menthol → HCID 69564003, compound

HRID 2253346Notes

Reaction equation

HRID 2253346 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:15])[C:10](OCC)=[O:11])=[CH:5][CH:4]=1)#[N:2].[CH3:16][C@H:17]1[CH2:22][C@@H:21]([OH:23])[C@H:20]([CH:24]([CH3:26])[CH3:25])[CH2:19][CH2:18]1>CC(OC)(C)C.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9](=[O:15])[C:10]([O:23][C@@H:21]2[CH2:22][C@H:17]([CH3:16])[CH2:18][CH2:19][C@H:20]2[CH:24]([CH3:26])[CH3:25])=[O:11])=[CH:7][CH:8]=1)#[N:2]

Participants

5

Reactant 2

HCID 16666(-)-MentholHCID 4065229Ethyl 4-cyanobenzoylformate

Product 1

HCID 69564003HCID 69564003, compoundYield 92.2%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl (4-cyanophenyl)(oxo)acetate (35.2 g, 173 mmol), (1R,2S,5R)-(−)-menthol (41.0 g, 262 mmol), and titanium ethoxide (3.6 mL, 17 mmol) was heated to 80° C. under vacuum for 60 hours. The mixture was diluted with MTBE (1.5 L), washed sequentially with 10% HCl (2×300 mL), saturated aqueous NaHCO3, and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 2% ethyl acetate/hexanes to provide the desired product (50.0 g, 92% yield). 1H NMR (CDCl3) δ 8.12 (m, 2H), 7.82 (m, 2H), 5.01 (ddd, 2H), 2.15 (m, 1H), 1.91 (m, 1H), 1.72 (m, 2H), 1.55 (m, 2H), 1.16 (m, 2H), 0.97(d, 3H), 0.91 (d, 3H), 0.83 (d, 3H).

Workup

  1. washwashed sequentially with 10% HCl (2×300 mL), saturated aqueous NaHCO3, and brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe concentrate was purified by flash column chromatography on silica gel with 2% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b4b3881e7b344e30849cc85d3d23c607
Source dataset
uspto-grants-2008_01
Patent number
US07323570B2

Reaction notes

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