Acetic Acid → HCID 57718984, compound

HRID 1985265Notes

Reaction equation

HRID 1985265 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH:5]([O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1)[CH3:6])[CH3:2].[CH2:19]([O:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH:30]=[O:31])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(O)(=O)C>C1COCC1.[NH4+].[Cl-]>[CH2:1]([O:3][C:4](=[O:18])[C:5]([CH3:6])([O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:16])([F:15])[F:17])=[CH:10][CH:9]=1)[CH:30]([C:29]1[CH:32]=[CH:33][CH:34]=[C:27]([O:26][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:28]=1)[OH:31])[CH3:2]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 743423-BenzyloxybenzaldehydeHCID 57719050HCID 57719050, compound

Product 1

HCID 57718984HCID 57718984, compoundYield 48.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-78 °C

Procedure

A −78° C. solution of 2-(4-trifluoromethyl-phenoxy)-propionic acid ethyl ester (10.0 g, 38.1 mmol) in THF (80 mL) was transferred via cannula to a −78° C. solution of 1.5 M LDA-THF complex (45.8 mL, 68.7 mmol) in THF (80 mL). The resultant mixture was stirred for 5 minutes at −78° C. and then 3-benzyloxybenzaldehyde (7.3 g, 34.4 mmol) was added in one portion and the reaction mixture stirred at −78° C. for 5 minutes and was then was quenched with a −78° C. THF solution of acetic acid (6.82 g, 113.5 mmol). The reaction mixture was diluted with aqueous saturated NH4Cl and extracted with Et2O. The organic layer was dried (Na2SO4) and the solvent removed in vacuo to afford 19.84 g of crude product that was purified by flash chromatography using 8:1 then 4:1 hexanes:acetone to afford 7.88 g (44%) 3-(3-benzyloxy-phenyl)-3-hydroxy-2-methyl-2-(4-trifluoromethyl-phenoxy)-propionic acid ethyl ester as a mixture of diasteriomers. Rf=0.55 (1:1 hexanes:acetone). 1NMR.

Workup

  1. customwas transferred via cannula to a −78° C.
  2. customwas then was quenched with a −78° C
  3. extractionextracted with Et2O
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customthe solvent removed in vacuo
  6. customto afford 19.84 g of crude product that
  7. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-91d08bd9d6344ebfbe6e79b4b5ee2080
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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