Reaction #87490

Reaction equation

(1S,2S,3S,4R,5S)-5-[4-Chloro-3-(4-ethoxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol

acetyl chloride

methanol

→

product

Yield 87.0%

Acetic acid (1R,2S,3S,4R,5S)-5-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-2,3,4-trihydroxy-6,8-dioxa-bicyclo[3.2.1]oct-1-ylmethyl ester

Yield 87.0%

Solvents

collidine

Conditions

Workup

1. 1
   ConcentrationThe crude mixture was concentrated under reduced pressure
2. 2
   OtherThe crude material was purified by flash chromatography over silica gel using the biotage
3. 3
   Washeluting with a gradient of 0 to 15% methanol in dichloromethane

Procedure

To a vigorously stirred solution of (1S,2S,3S,4R,5S)-5-[4-Chloro-3-(4-ethoxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol (1A, 0.481 g, 1.1 mmol) in collidine (2.5 mL) cooled to −35 degrees Celsius was added drop-wise over 10 minutes acetyl chloride (0.149 mL, 2.1 mmol). After 1 hour, methanol (0.5 mL) was added and the reaction mixture was allowed to warm to room temperature. The crude mixture was concentrated under reduced pressure and codistilled three times with toluene. The crude material was purified by flash chromatography over silica gel using the biotage automated chromatography unit (50 g silica gel column) and eluting with a gradient of 0 to 15% methanol in dichloromethane. 456 mg (87% yield) of product obtained as a white solid.

Source