HCID 16216227, compound → HCID 16216229, compound

HRID 628192Notes

Reaction equation

HRID 628192 reaction equation
Cl[C:2](Cl)(Cl)[C:3](=N)[O:4][CH:5]1[O:30][C@H:29]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@@H:15]([O:16][P:17]2(=[O:28])[O:23][CH2:22][C:21]3[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=3[CH2:19][O:18]2)[C@H:7]([O:8][C:9]([O:11][CH2:12][CH:13]=[CH2:14])=[O:10])[C@H:6]1[NH:40][C:41]([O:43][CH2:44][CH:45]1[C:57]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[C:51]2[C:46]1=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:42].[N:61]([C@@H:64]1[C@@H:77]([OH:78])[C@H:76]([O:79][CH2:80][C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)[C@@H](CO)[O:74][C@H:65]1[O:66][Si:67]([C:70]([CH3:73])([CH3:72])[CH3:71])([CH3:69])[CH3:68])=[N+:62]=[N-:63]>C(Cl)Cl.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>[CH2:12]([O:11][C:9]([O:8][C@H:7]1[C@H:15]([O:16][P:17]2(=[O:28])[O:18][CH2:19][C:24]3[CH:25]=[CH:26][CH:27]=[CH:20][C:21]=3[CH2:22][O:23]2)[C@@H:29]([CH2:31][O:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[O:30][C@@H:5]([O:4][CH2:3][C@H:2]2[O:74][C@@H:65]([O:66][Si:67]([C:70]([CH3:73])([CH3:72])[CH3:71])([CH3:69])[CH3:68])[C@H:64]([N:61]=[N+:62]=[N-:63])[C@@H:77]([OH:78])[C@@H:76]2[O:79][CH2:80][C:81]2[CH:82]=[CH:83][CH:84]=[CH:85][CH:86]=2)[C@@H:6]1[NH:40][C:41]([O:43][CH2:44][CH:45]1[C:57]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[C:51]2[C:46]1=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:42])=[O:10])[CH:13]=[CH2:14]

Participants

5

Reactant 2

HCID 16216227HCID 16216227, compoundHCID 16216228HCID 16216228, compound

Product 1

HCID 16216229HCID 16216229, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 65367Trimethylsilyl triflateCatalystHCID 6344DichloromethaneSolvent

Procedure

A suspension of trichloroacetimidate 12 (1.04 g, 1.21 mmol), acceptor 8 (740 mg, 1.82 mmol) and molecular sieves (4 Å, 500 mg) in DCM (20 mL) was stirred at room temperature for 1 h. The mixture was cooled (−60° C.) and then TMSOTf (18 μL, 0.09 mmol) was added. After stirring the reaction mixture for 15 min, it was quenched with solid NaHCO3. The solids were removed by filtration, and the filtrate was washed with saturated aqueous NaHCO3 (2×50 mL) and brine (2×40 mL). The organic phase was dried (MgSO4) and filtered. Next, the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/ethyl acetate, 2/1, v/v) to give 13 as a colorless solid (1.09 g, 79%). Rf=0.37 (DCM/methanol, 50/1, v/v). [α]26D 3.8 (c=1.0, CHCl3). 1H NMR (600 MHz, CD3COCD3): δ 7.84-7.20 (m, 22H, aromatic), 6.98 (d, 1H, JNH′,2′=9.0 Hz, NH′), 5.83 (m, 1H, OCH2CH═CH2), 5.41 (t, 1H, J2′,3′=J3′,4′=9.6 Hz, H-3′,), 5.29-5.21 (m, 3H, OCH2CH═CH2, C6H4(CH2O)2P), 5.13-5.03 (m, 3H, H-1′, OCH2CH═CH2, C6H4(CH2O)2P), 4.96-4.91 (m, 2H, CH2aPh, C6H4(CH2O)2P), 4.73-4.45 (m, 7H, H-1, H-4′, CH2bPh, CH2Ph, OCH2CH═CH2), 4.24-4.13 (m, 4H, H-6, CO2CH2, Fmoc, CO2CH2CH, Fmoc), 3.93-3.79 (m, 4H, H-5′, H-6a, H-6′a, H-6′b), 3.69 (m, 1H, H-2′), 3.54 (broad, 3H, H-3, H-4, H-5), 3.19 (dd, 1H, J1,2=7.8 Hz, J2,3=9.0 Hz, H-2), 0.92 (s, 9H, SiC(CH3)3), 0.17 (s, 6H, Si(CH3)2). 13C NMR (75 MHz, CD3COCD3): δ 156.39 (C═O), 155.28 (C═O), 144.96-120.56 (aromatic, OCH2CH═CH2), 118.41 (OCH2CH═CH2), 101.14 (C-1′), 97.33 (C-1), 78.54, 77.87, 75.72, 75.25-74.42 (m), 73.83, 70.35, 69.52, 69.04-68.73 (m), 67.91, 67.12, 57.03 (C-2′), 47.64 (CO2CH2, Fmoc), 25.83 (SiC(CH3)3), 18.27 (SiC(CH3)3), −3.85 (Si(CH3)2), −5.21 (Si(CH3)2). HR MS (m/z) calculated for C59H69N4O16PSi[M+Na]+, 1171.4113. found, 1171.4256.

Workup

  1. temperatureThe mixture was cooled (−60° C.)
  2. stirringAfter stirring the reaction mixture for 15 min
  3. customit was quenched with solid NaHCO3
  4. customThe solids were removed by filtration
  5. washthe filtrate was washed with saturated aqueous NaHCO3 (2×50 mL) and brine (2×40 mL)
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationNext, the filtrate was concentrated in vacuo
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate, 2/1

Sources & evidence

ORD record
ord-ab9fef60cec94224a7400720ff8a9d18
Source dataset
uspto-grants-2016_04
Patent number
US09309276B2

Reaction notes

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