Reaction #2286293

Reaction equation

hydrochloric acid

lithium aluminum hydride

(3,5-dichloro-4-hydroxy-phenyl)-acetic acid methyl ester

(3,5-Dichloro-4-hydroxy-phenyl)-acetic acid methyl ester

→

2,6-dichloro-4-(2-hydroxy-ethyl)-phenol

Yield 100.1%

2,6-Dichloro-4-(2-hydroxy-ethyl)-phenol

Yield 100.1%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.ADDITIONafter the addition
2. 2
   Otherwas quenched at −10° C. by the dropwise addition of a 10% aqueous Rochelle's Salt solution (80 mL)
3. 3
   workup.STIRRINGThe reaction suspension was stirred 10 min
4. 4
   workup.ADDITIONEthyl acetate (100 mL) was then added to the suspension
5. 5
   FiltrationThe mixture was then filtered
6. 6
   WashThe solids were rinsed with ethyl acetate (2×500 mL)
7. 7
   OtherThe organic layer was separated
8. 8
   ExtractionThe aqueous layer was extracted with ethyl acetate (2×200 mL)
9. 9
   Washwashed with a 0.1N aqueous hydrochloric acid solution, water
10. 10
    DryingThe organic layer was dried with magnesium sulfate
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated
13. 13
    Otherto afford the first crop of solid
14. 14
    Otherwas placed under high vacuum overnight
15. 15
    Extractionwas then re-extracted with ethyl acetate (3×200 mL)
16. 16
    Washwashed with water
17. 17
    DryingThe organic layer was dried with magnesium sulfate
18. 18
    Filtrationfiltered
19. 19
    Concentrationconcentrated
20. 20
    Otherwas placed under high vacuum overnight

Procedure

A solution of (3,5-dichloro-4-hydroxy-phenyl)-acetic acid methyl ester (15) (15.7 g, 67.09 mmol) in anhydrous tetrahydrofuran (600 mL) under argon cooled to −10° C. was treated slowly dropwise with a 1 M solution of lithium aluminum hydride in tetrahydrofuran (67.1 mL, 67.1 mmol). The reaction mixture was stirred for 5 min after the addition was complete and was quenched at −10° C. by the dropwise addition of a 10% aqueous Rochelle's Salt solution (80 mL). The reaction suspension was stirred 10 min. Ethyl acetate (100 mL) was then added to the suspension. The mixture was then filtered. The solids were rinsed with ethyl acetate (2×500 mL). The organic layer was separated. The aqueous layer was extracted with ethyl acetate (2×200 mL). The organic layers were combined and washed with a 0.1N aqueous hydrochloric acid solution, water, and a saturated aqueous sodium chloride solution. The organic layer was dried with magnesium sulfate, filtered and concentrated to afford the first crop of solid. The resulting solid was placed under high vacuum overnight. The aqueous layer was acidified to pH=5 by the addition of a 1N aqueous hydrochloric acid solution and was then re-extracted with ethyl acetate (3×200 mL). The organic layers were combined and washed with water and a saturated aqueous sodium chloride solution. The organic layer was dried with magnesium sulfate, filtered and concentrated. The resulting solid was placed under high vacuum overnight to afford 2,6-dichloro-4-(2-hydroxy-ethyl)-phenol (16) (13.9 g, 100%); LRMS for C8H8Cl2O2 (M+) m/z=207 Molecular Weight=207.0578; Exact Mass=205.9901

Source