반응 #89635

반응 방정식

(3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide

HCl

acetic acid

→

(3R,4S)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid

수율 79.0%

용매

water

water

반응 조건

후처리

1. 1
   기타capped
2. 2
   온도cooled to room temperature
3. 3
   추출extracted with methylene chloride (20 mL)
4. 4
   농축concentrated
5. 5
   workup.ADDITIONThe residue was treated with water (20 mL)
6. 6
   농축concentrated three times
7. 7
   기타to remove excess HCl
8. 8
   workup.DISSOLUTIONdissolved in water (40 mL)
9. 9
   workup.ADDITIONtreated with DOWEX® 550A-OH resin (3 g) which
10. 10
    세척had been rinsed with methanol
11. 11
    workup.STIRRINGThe mixture was stirred for 40 min
12. 12
    여과filtered
13. 13
    세척the resin washed successively with water, methanol, methylene chloride, water, methanol, and methylene chloride
14. 14
    workup.STIRRINGThe resin was then stirred four times with 1N HCl (15 mL)
15. 15
    여과filtered
16. 16
    농축the combined filtrates were concentrated
17. 17
    workup.ADDITIONThe residue was treated with water (20 mL)
18. 18
    농축concentrated three times
19. 19
    기타to remove excess HCl
20. 20
    workup.DISSOLUTIONdissolved in 1.5-2.0 mL water
21. 21
    기타subjected to HPLC gradient purification
22. 22
    농축The appropriate fractions were concentrated
23. 23
    workup.ADDITIONtreated three times with 1 N HCl (10 mL)
24. 24
    농축concentrated
25. 25
    workup.ADDITIONtreated three times with water (10 mL)
26. 26
    농축concentrated
27. 27
    workup.DISSOLUTIONdissolved in water (10 mL)
28. 28
    온도frozen
29. 29
    workup.WAITlyophilized overnight

실험 절차

A solution of (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (198 mg, 0.5 mmol) in 2:1:1 concentrated HCl:glacial acetic acid:water (8 mL) in a pressure bottle was stirred for 2 h at 60° C., then capped and stirred for 18 h at 130° C., cooled to room temperature, and uncapped. The solution was diluted with water (20 mL), then extracted with methylene chloride (20 mL) and concentrated. The residue was treated with water (20 mL) and concentrated three times to remove excess HCl, then dissolved in water (40 mL) and treated with DOWEX® 550A-OH resin (3 g) which had been rinsed with methanol. The mixture was stirred for 40 min, then filtered and the resin washed successively with water, methanol, methylene chloride, water, methanol, and methylene chloride. The resin was then stirred four times with 1N HCl (15 mL) and filtered, and the combined filtrates were concentrated. The residue was treated with water (20 mL) and concentrated three times to remove excess HCl, then dissolved in 1.5-2.0 mL water and subjected to HPLC gradient purification as follows: 0-25% B with A=0.1% trifluoroacetic acid/water and B=0.1% trifluoroacetic acid/acetonitrile. The appropriate fractions were concentrated, treated three times with 1 N HCl (10 mL) and concentrated, treated three times with water (10 mL) and concentrated, then dissolved in water (10 mL), frozen, and lyophilized overnight to afford (3R,4S)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (114 mg, 79%) as a pale amber glass. NMR (D2O) δ 3.90 (d, J=13 Hz, 1 H), 3.71 (dd, J111.5 Hz, J2=8.5 Hz, 1 H), 3.46 (d, J=13 Hz, 1 H), 3.21 (t, J=12 Hz, 1 H), 2.50-2.65 (m, 1 H), 1.5-1.65 (m, 1 H), 1.10-1.40 (m, 3 H), 0.60-0.75 (m, 2 H). MS (m+1): 217.3; MS (m−H2O+1): 199.1.

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