Reaction #57418

Reaction equation

sodium

dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid

sodium

NaOH

HCl

dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid

NaOH

NaHCO3

dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid

Formula IX

dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid

NaHCO3

NaHCO3

CO2

→

a-oxotricyclo[3.3.1.13,7]decane-1-acetic acid

3-Hydroxy-α-oxotricyclo-[3.3.1.13,7]decane-1-acetic acid

Solvents

water

Conditions

Workup

1. 1
   Otherto give a hazy solution
2. 2
   OtherThe reaction vessel was fitted with a reflux condenser/argon inlet
3. 3
   TemperatureAfter heating for approximately 6 hours the mixture
4. 4
   Temperatureto cool to room temperature
5. 5
   ExtractionThe resulting mixture was extracted with ethyl acetate (4×300 ml)
6. 6
   ExtractionThe aqueous layer (pH 0.37) after the first extraction with ethyl acetate
7. 7
   workup.ADDITIONwas lowered to pH 0.18 by the addition of concentrated HCl (approximately 2 ml)
8. 8
   Washwashed with brine (100 ml)
9. 9
   DryingAfter drying over anhydrous magnesium sulfate
10. 10
    Otherthe solvent was removed at reduced pressure

Procedure

A 500 ml three-necked flask was charged with dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid (Formula IX) (38.67 g, 138.5 mmol). To this material was added water (160 ml) and 1 N NaOH (138 ml, 138 mmol; 1 N NaOH was used to generate the sodium salt of dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid to avoid foaming problems which would occur with solid NaHCO3) to give a hazy solution. To this solution was added solid NaHCO3 (29.10 grams, 346 mmol, 2.50 equivalents). After the NaHCO3 was added the reaction mixture became a suspension as the sodium salt of dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid was forced from solution. The reaction vessel was fitted with a reflux condenser/argon inlet and heated to approximately 80° C. After heating for approximately 6 hours the mixture was allowed to cool to room temperature. The reaction mixture (pH 7.22) was carefully acidified (CO2 evolution) to pH 0.15 by the addition of concentrated HCl (32 ml required). The resulting mixture was extracted with ethyl acetate (4×300 ml). The aqueous layer (pH 0.37) after the first extraction with ethyl acetate was lowered to pH 0.18 by the addition of concentrated HCl (approximately 2 ml). The ethyl acetate fractions were combined and washed with brine (100 ml). After drying over anhydrous magnesium sulfate, the solvent was removed at reduced pressure to give 3-hydroxy-<a-oxotricyclo[3.3.1.13,7]decane-1-acetic acid (Formula II) as a colorless granular solid: 30.77 gram (99%).

Source