反応 #87477

反応方程式

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

収率 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

収率 93.0%

溶媒

methanol

反応条件

後処理

1. 1
   その他the reaction was quenched by the addition of water (20 mL)
2. 2
   濃縮the resulting mixture was concentrated under reduced pressure
3. 3
   抽出The resulting aqueous layer was extracted three times with ethyl acetate (15 mL)
4. 4
   洗浄The combined organic layers were washed with brine
5. 5
   乾燥dried over sodium sulfate
6. 6
   ろ過filtered
7. 7
   濃縮concentrated 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
   その他was obtained
10. 10
    workup.WAITAfter 16 hours
11. 11
    洗浄was washed with methanol 3 times before use) until the pH of the solution
12. 12
    ろ過The reaction mixture was filtered
13. 13
    濃縮concentrated under reduced pressure
14. 14
    その他The resulting material was precipitated from ethyl acetate and heptane
15. 15
    洗浄The resulting solid was washed with heptane 2 times
16. 16
    その他dried under reduced pressure

実験手順

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).

出典