Reaction #87477

Reaction equation

acetic acid (1R,2S,3S,4R,5S)-3,4-diacetoxy-1-acetoxymethyl-5-[4-chloro-3-(4-ethoxy-benzoyl)-phenyl]-6,8-dioxa-bicyclo[3.2.1]oct-2-yl ester

sodium borohydride

→

desired product

Yield 93.0%

(1S,2S,3S,4R,5S)-5-{4-chloro-3-[(4-ethoxy-phenyl)-hydroxy-methyl]-phenyl}-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol

Yield 93.0%

Solvents

methanol

Conditions

Workup

1. 1
   Otherthe reaction was quenched by the addition of water (20 mL)
2. 2
   Concentrationthe resulting mixture was concentrated under reduced pressure
3. 3
   ExtractionThe resulting aqueous layer was extracted three times with ethyl acetate (15 mL)
4. 4
   WashThe combined organic layers were washed with brine
5. 5
   Dryingdried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   workup.ADDITIONTo a solution of this crude material in methanol (5 mL) was added sodium methoxide in methanol (25% wt) until pH 12
9. 9
   Otherwas obtained
10. 10
    workup.WAITAfter 16 hours
11. 11
    Washwas washed with methanol 3 times before use) until the pH of the solution
12. 12
    FiltrationThe reaction mixture was filtered
13. 13
    Concentrationconcentrated under reduced pressure
14. 14
    OtherThe resulting material was precipitated from ethyl acetate and heptane
15. 15
    WashThe resulting solid was washed with heptane 2 times
16. 16
    Otherdried under reduced pressure

Procedure

To a solution of acetic acid (1R,2S,3S,4R,5S)-3,4-diacetoxy-1-acetoxymethyl-5-[4-chloro-3-(4-ethoxy-benzoyl)-phenyl]-6,8-dioxa-bicyclo[3.2.1]oct-2-yl ester (see Example 11 for preparation; 85 mg, 0.14 mmol) in methanol (3 mL) was added sodium borohydride (25 mg, 0.66 mmol) at room temperature. After one hour, the reaction was quenched by the addition of water (20 mL) and the resulting mixture was concentrated under reduced pressure. The resulting aqueous layer was extracted three times with ethyl acetate (15 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. To a solution of this crude material in methanol (5 mL) was added sodium methoxide in methanol (25% wt) until pH 12 was obtained and the resulting mixture was stirred at room temperature. After 16 hours, the reaction mixture was neutralized by the addition of Dowex Monosphere 650C (H) cation exchange resin (the resin was washed with methanol 3 times before use) until the pH of the solution was <7. The reaction mixture was filtered and concentrated under reduced pressure. The resulting material was precipitated from ethyl acetate and heptane. The resulting solid was washed with heptane 2 times and dried under reduced pressure to yield the desired product (58.9 mg, 93% yield) as a white solid. MS (LCMS) 497.3 (M−HCOO−, negative mode)1H NMR (400 MHz, METHANOL-d4) delta ppm 1.33 (t, J=6.9 Hz, 6 H), 3.56 (d, J=8.0 Hz, 1 H), 3.59-3.64 (m, 3 H), 3.64-3.69 (m, 2 H), 3.68 (d, J=12.5 Hz, 2 H), 3.78 (d, J=8.2 Hz, 2 H), 3.84 (d, J=12.5 Hz, 2 H), 3.98 (q, J=7.0 Hz, 4 H), 4.15 (d, J=7.4 Hz, 1 H), 4.16 (d, J=7.4 Hz, 1 H), 6.04 (s, 1 H), 6.05 (s, 1 H), 6.80 (d, J=8.4 Hz, 4 H), 7.21 (d, J=8.6 Hz, 2 H), 7.22 (d, J=8.6 Hz, 2 H), 7.29 (d, J=8.2 Hz, 2 H), 7.40-7.42 (m, 2 H), 7.91 (d, J=2.0 Hz, 1 H), 7.93 (d, J=2.0 Hz, 1 H).

Source