Hydrochloric Acid → 2-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexylmethylene]-succinic acid 1-methyl ester

HRID 426427Notes

Reaction equation

HRID 426427 reaction equation
[C:1]([O:9]C)(=[O:8])[CH2:2][CH2:3][C:4]([O:6][CH3:7])=[O:5].[C:11]([Si:15]([CH3:26])([CH3:25])[O:16][CH:17]1[CH2:22][CH2:21][CH:20]([CH:23]=O)[CH2:19][CH2:18]1)([CH3:14])([CH3:13])[CH3:12].CC(C)([O-])C.[K+].C(O)(C)(C)C.Cl>>[CH3:7][O:6][C:4](=[O:5])[C:3](=[CH:23][CH:20]1[CH2:19][CH2:18][CH:17]([O:16][Si:15]([C:11]([CH3:12])([CH3:14])[CH3:13])([CH3:26])[CH3:25])[CH2:22][CH2:21]1)[CH2:2][C:1]([OH:9])=[O:8]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 7820Dimethyl SuccinateHCID 22167749HCID 22167749, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 667020492-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexylmethylene]-succinic acid 1-methyl esterYield 38.3%

Conditions

Temperature
50 °C

Procedure

A solution of dimethyl succinate (730 mg, 5.0 mmol) and 4-(tert-butyl-dimethyl-silanyloxy)-cyclohexanecarbaldehyde (1.00 g, 4.1 mmol) was added over 25 min to a 1.0M solution of potassium tert-butoxide in tert-butanol (4.4 mL. 4.4 mmol). The reaction mixture was heated at 50° C. for 50 min, cooled to RT and concentrated under vacuum. The residue was dissolved in water (25 mL) and washed with EtOAc (2×10 mL). The aqueous layer was acidified with 6 N HCl (2.0 mL, 12 mmol) and extracted with EtOAc (2×20 mL), dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (25% EtOAc/DCM) to give the title compound (560 mg) as a mixture of olefin isomers (˜1:1) and a mixture of cis and trans isomers at the cyclohexyl ring (˜1:1). 1H NMR (CDCl3, 400 mHz) δ (ppm) olefin peaks at 6.88 (d, J=10.2 Hz) 6.77 (d, J=10.0 Hz) CHOTBS peaks at 3.96 ppm (br s) (cis isomer, hydrogen equitorial, 3.55 (m) (trans isomer, hydrogen axial).

Workup

  1. temperaturecooled to RT
  2. concentrationconcentrated under vacuum
  3. dissolutionThe residue was dissolved in water (25 mL)
  4. washwashed with EtOAc (2×10 mL)
  5. extractionextracted with EtOAc (2×20 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (25% EtOAc/DCM)

Sources & evidence

ORD record
ord-fcbe913322c4473d90e499383c6ad34f
Source dataset
uspto-grants-2012_01
Patent number
US08106232B2

Reaction notes

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