Benzoyl chloride → HCID 68653431, compound

HRID 2179126Notes

Reaction equation

HRID 2179126 reaction equation
[C:1]([NH:6][C:7]1[C:8]2[N:9]=[CH:10][N:11]([C:43]=2[N:44]=[CH:45][N:46]=1)[C@:12]1(C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[O:23][C@H:18]([CH2:19][O:20]OC)[C@@H:16]([OH:17])[C@H:13]1[O:14][CH3:15])(=[O:5])[CH2:2][CH2:3][CH3:4].[C:47](Cl)(=[O:54])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>N1C=CC=CC=1>[C:47]([O:17][C@@H:16]1[C@@H:18]([CH2:19][OH:20])[O:23][C@@H:12]([N:11]2[C:43]3[N:44]=[CH:45][N:46]=[C:7]([NH:6][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])[C:8]=3[N:9]=[CH:10]2)[C@@H:13]1[O:14][CH3:15])(=[O:54])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

4

Reactant 2

HCID 7412Benzoyl chlorideHCID 86660148HCID 86660148, compound

Product 1

HCID 68653431HCID 68653431, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

N-Butyryl-5′-O-monomethoxytrityl-2′-O-methyladenosine 7 (100 mg, 0.16 mmol) was dried by evaporation of added dry pyridine (5 mL) under reduced pressure and finally by keeping on a vacuum pump for 30 min. Dry pyridine was added (2 mL) and the solution was put into ice-bath whereupon benzoyl chloride was added (1.2 eq, 0.19 mmol, 22.2 μL) and after 10 min the ice-bath was removed and the reaction was allowed to warm up and was then left stirring overnight at room temperature. A small amount of NaHCO3 (aq. sat.) was added and the solvent was evaporated under reduced pressure. Dichloromethane was added and the organic phase was washed with NaHCO3 (aq. sat. 2×). The organic phase was collected, dried (MgSO4), filtered and concentrated. Evaporation of added toluene (2×) and dichloromethane (2×) was done to remove traces of pyridine. The remaining crude material of compound 8 was dissolved in 80% acetic acid (10 mL) and allowed to react at room temperature for 4 h. after which deprotection of 5′-monomethoxytrityl was complete (TLC, mass). The solution was concentrated and added toluene (2×) and dichloromethane (2×) evaporated under reduced pressure to remove excess acetic acid. The compound was purified on silica gel column chromatography using a gradient of methanol in dichloromethane (0-5%). Yield 80% of compound 9. 1H NMR (CDCl3) δ 1.04 (3H, t, J=7.4 Hz), 1.80 (2H, m), 2.92 (2H, t, J=7.4 Hz), 3.31 (3H, s), 3.96 (2H, m), 4.51 (1H, s), 4.87 (1H, m), 5.90 (1H, d, J=4.9 Hz), 6.01 (1H, d, J=7.9 Hz), 6.32 (1H, d, J=9.9 Hz), 7.27 (2H, m), 7.51 (1H, m), 8.12 (2H, m), 8.18 (1H, s), 8.70 (1H, s), 9.27 (1H, s), 13C NMR δ 13.9, 18.4, 40.0, 59.3, 63.1, 72.7, 77.4, 81.4, 86.8, 89.9, 123.7, 128.1, 128.9, 129.8, 133.7, 143.5, 150.2, 152.1, 165.8, 173.5, MS (ES-TOF) m/z calculated: 455.18. found: 455.38.

Workup

  1. additionwas added (1.2 eq, 0.19 mmol, 22.2 μL)
  2. customafter 10 min the ice-bath was removed
  3. temperatureto warm up
  4. waitwas then left
  5. additionA small amount of NaHCO3 (aq. sat.) was added
  6. customthe solvent was evaporated under reduced pressure
  7. additionDichloromethane was added
  8. washthe organic phase was washed with NaHCO3 (aq. sat. 2×)
  9. customThe organic phase was collected
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customEvaporation of added toluene (2×) and dichloromethane (2×)
  14. customto remove traces of pyridine
  15. dissolutionThe remaining crude material of compound 8 was dissolved in 80% acetic acid (10 mL)
  16. customto react at room temperature for 4 h. after which deprotection of 5′-monomethoxytrityl
  17. concentrationThe solution was concentrated
  18. additionadded toluene (2×) and dichloromethane (2×)
  19. customevaporated under reduced pressure
  20. customto remove excess acetic acid
  21. customThe compound was purified on silica gel column chromatography

Sources & evidence

ORD record
ord-3ad2dbbc268548b9a8379038c77f9b77
Source dataset
uspto-grants-2015_06
Patent number
US09067964B2

Reaction notes

Loading…