Pyridine → HCID 86658277, compound

HRID 74839Notes

Reaction equation

HRID 74839 reaction equation
[C:1]([O:9][C@H:10]1[C@@H:15]([OH:16])[C@H:14]([O:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@@H:13]([CH2:26][O:27][C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:12][C@@H:11]1[O:36][C@H:37]1[C@H:50]([O:51][C:52](=[O:59])[C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[C@@H:49]([CH2:60][O:61][C:62](=[O:69])[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[O:48][C@H:39]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C@H:38]1[O:70][C:71](=[O:78])[C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(Cl)(Cl)C(=N)O[C@H:83]1[O:115][C@H:114]([CH2:116][O:117][C:118](=[O:125])[C:119]2[CH:124]=[CH:123][CH:122]=[CH:121][CH:120]=2)[C@@H:104]([O:105][C:106](=[O:113])[C:107]2[CH:112]=[CH:111][CH:110]=[CH:109][CH:108]=2)[C@H:94]([O:95][C:96](=[O:103])[C:97]2[CH:102]=[CH:101][CH:100]=[CH:99][CH:98]=2)[C@@H:84]1[O:85][C:86](=[O:93])[C:87]1[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.N1C=CC=CC=1.C(Cl)(=O)C1C=CC=CC=1>C(Cl)Cl.CCN(CC)CC>[C:86]([O:85][C@H:84]1[C@@H:94]([O:95][C:96](=[O:103])[C:97]2[CH:102]=[CH:101][CH:100]=[CH:99][CH:98]=2)[C@H:104]([O:105][C:106](=[O:113])[C:107]2[CH:108]=[CH:109][CH:110]=[CH:111][CH:112]=2)[C@@H:114]([CH2:116][O:117][C:118](=[O:125])[C:119]2[CH:120]=[CH:121][CH:122]=[CH:123][CH:124]=2)[O:115][C@@H:83]1[O:16][C@H:15]1[C@H:14]([O:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@@H:13]([CH2:26][O:27][C:28](=[O:35])[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[O:12][C@H:11]([O:36][C@H:37]2[C@H:50]([O:51][C:52](=[O:59])[C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=3)[C@@H:49]([CH2:60][O:61][C:62](=[O:69])[C:63]3[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=3)[O:48][C@H:39]([O:40][CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C@H:38]2[O:70][C:71](=[O:78])[C:72]2[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=2)[C@H:10]1[O:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:93])[C:87]1[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 7412Benzoyl chlorideHCID 65367Trimethylsilyl triflateHCID 10963703alpha-D-Mannopyranose, 2,3,4,6-tetrabenzoate 1-(2,2,2-trichloroethanimidate)HCID 86658275Benzyl 2,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1->3)-2,4,6-tri-O-benzoyl-alpha-D-mannopyranoside

Product 1

HCID 86658277HCID 86658277, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

A solution of the alcohol 50 (424 mg, 0.401 mmol) and 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate (357 mg, 0.481 mmol, 1.2 eq) in anhydrous DCM (7.5 mL) was stirred with powdered molecular sieves 3 Å (50 mg) at 0° C. for 1 h. A solution of TMSOTf (15 μL, 0.0802 mmol, 0.2 eq) in DCM (0.5 mL) was added dropwise via a syringe. The mixture was stirred at 0° C. for 2 h and TLC indicated complete conversion. Et3N (100 μL) was added. Pyridine (65 μL, 0.802 mmol) and benzoyl chloride (47 μL, 0.401 mmol) were added. The mixture was stirred at room temperature o/n and evaporated onto silica gel. Purification by column chromatography (silica 2.5×17 cm, gradient elution with hexane-EtOAc 210:30, 200:50, 180:60, 160:80 and 150:100) gave the trisaccharide 51 as a colourless gum (392 mg, 60%). 1H NMR (CDCl3, 400 MHz) δ 8.19-7.89 (m, 16H, Ph), 7.68-7.63 (m, 4H, Ph), 7.61-7.15 (m, 35H, Ph), 6.00 (dd or t, 1H, JH3-H4=10.7, JH4-H5=9.8, H4), 5.98 (dd or t, 1H, JH3-H4=9.8, J=9.8, H4), 5.92 (dd or t, 1H, J=10.7, J=9.8, H4), 5.72 (dd, 1H, JH1-H2=2.0, JH2-H3=3.9, H2), 5.56 (dd, 1H, JH2-H3=2.9, H3), 5.33 (d, 1H, J=2.0, H1), 5.26 (dd, 1H, J=2.0, H2), 5.19 (d, 1H, J=2.0, J=3.9, H2), 5.16 (d, 1H, J=2.0, H1), 4.90 (d, 1H, H1), 4.78 and 4.62 (AB quartet, 2H, Jgem=11.7, CH2), 4.65-4.56 (m, 3H), 4.45 (dd, 1H, Jgem=12.7, JH5-H6=3.9, H6), 4.35 (dd, 1H, H3), 4.34-4.28 (m, 2H), 4.24 (dd, 1H, J=12.7, JH5-H6=2.9, H6), 4.10 (dt or dm, 1H, H5), 4.01 (dd, 1H, J=12.7, H6), 3.95 (dd, 1H, JH5-H6=2.0, H6).

Workup

  1. stirringThe mixture was stirred at room temperature o/n and
  2. customevaporated onto silica gel
  3. customPurification
  4. washby column chromatography (silica 2.5×17 cm, gradient elution with hexane-EtOAc 210:30, 200:50, 180:60, 160:80 and 150:100)

Sources & evidence

ORD record
ord-f488dd4163d54d7e958e7cbf9d3fb91c
Source dataset
uspto-grants-2014_09
Patent number
US08828952B2

Reaction notes

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