Acetic Acid → 3-(4-Benzyloxy-phenyl)-3-hydroxy-2-methyl-2-o-tolyloxy-propionic Acid Ethyl Ester

HRID 585280Notes

Reaction equation

HRID 585280 reaction equation
[Li+].CC([N-]C(C)C)C.[CH2:9]([O:11][C:12](=[O:23])[CH:13]([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH3:22])[CH3:14])[CH3:10].[CH2:24]([O:31][C:32]1[CH:39]=[CH:38][C:35]([CH:36]=[O:37])=[CH:34][CH:33]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(O)(=O)C.[NH4+].[Cl-]>C1COCC1.C(OCC)C>[CH2:9]([O:11][C:12](=[O:23])[C:13]([CH3:14])([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH3:22])[CH:36]([C:35]1[CH:34]=[CH:33][C:32]([O:31][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[CH:39][CH:38]=1)[OH:37])[CH3:10]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 78109Benzaldehyde, 4-(phenylmethoxy)-HCID 2724682Lithium diisopropylamideHCID 10398141Ethyl 2-(2-methylphenoxy)propionate

Product 1

HCID 208231503-(4-Benzyloxy-phenyl)-3-hydroxy-2-methyl-2-o-tolyloxy-propionic Acid Ethyl EsterYield 54%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of LDA (34.9 mL, 52.4 mmol, 1.5M in cyclohexane) in anhydrous THF (60 mL) was cooled to −78° C. in a dry ice/acetone bath and added to a solution of 2-o-Tolyloxy-propionic acid ethyl ester in anhydrous THF (60 mL) also cooled to −78° C. under an atmosphere of nitrogen. After five minutes, 4-benzyloxybenzaldehyde (5.56 g, 26.2 mmol) was added in one portion. After stirring for one minute, the reaction mixture was quenched with acetic acid (5 mL, 87.4 mmol, d=1.049) and a saturated solution of aqueous NH4Cl (50 mL). The biphasic mixture was allowed to warm to room temperature and diluted with diethyl ether (1 L). The organic layer was washed with water, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash column chromatography (13% ethyl acetate in hexanes) to provide a mixture of diastereomers of the titled compound (6.36 g, 54%). 1H NMR (400 MHz, CDCl3): • 7.44-7.32 (m, 6H), 7.16-6.82 (m, 5H), 69.74-6.66 (m, 2H), 5.16 (d, 1H, J=3.52 Hz), 5.07 (s, 2H), 4.26-4.15 (m, 2H), 2.28 (s, 3H), 1.43 (s, 3H), 1.22-1.17 (m, 3H). Rf=0.25 in 25% ethyl acetate in hexanes.

Workup

  1. temperatureto warm to room temperature
  2. washThe organic layer was washed with water
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography (13% ethyl acetate in hexanes)
  6. customto provide

Sources & evidence

ORD record
ord-0fabf10d1f0a4086a617d9c9a3cf89d1
Source dataset
uspto-grants-2005_08
Patent number
US06930120B2

Reaction notes

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