Reaction #530917

Reaction equation

3,4-dimethoxyphenylacetic acid

EEDQ

α-(1-amino-1-methylethyl)-3-methoxybenzenemethanol

→

N-(β-hydroxy-3-methoxy-α,α-dimethylphenethyl)-3,4-dimethoxybenzeneacetamide

Yield 72.0%

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   OtherTetrahydrofuran is evaporated in vacuo
2. 2
   ExtractionThe amide is extracted twice with 500 ml
3. 3
   WashThe combined organic extracts are washed with 500 ml
4. 4
   Dryingdilute aqueous NH4OH solution, dried (Na2SO4)
5. 5
   Otherevaporated to dryness in vacuo
6. 6
   workup.DISSOLUTIONThe residual oil is dissolved in hot diethyl ether from which it
7. 7
   Othercrystallizes
8. 8
   Otherto give 72.0 g
9. 9
   OtherRecrystallization from diethyl ether
10. 10
    Othergives 70 g

Procedure

A solution of 50 g. (0.26 mole) of 3,4-dimethoxyphenylacetic acid, 68 g. (0.28 mole) of EEDQ and 50 g. (0.26 mole) of α-(1-amino-1-methylethyl)-3-methoxybenzenemethanol in 450 ml. tetrahydrofuran are stirred for three days at 25° C., and then heated for 5 hours at 65° C. Tetrahydrofuran is evaporated in vacuo, and the residue is taken up with ice and 10% aqueous H2SO4 solution to pH 2. The amide is extracted twice with 500 ml. ethyl acetate. The combined organic extracts are washed with 500 ml. dilute aqueous NH4OH solution, dried (Na2SO4) and evaporated to dryness in vacuo. The residual oil is dissolved in hot diethyl ether from which it crystallizes to give 72.0 g. of impure product. Recrystallization from diethyl ether gives 70 g. (72% yield) of N-(β-hydroxy-3-methoxy-α,α-dimethylphenethyl)-3,4-dimethoxybenzeneacetamide as white crystals of analytical purity, m.p. 137°-138° C.

Source