Chlorotrimethylsilane → HCID 118983440, compound

HRID 931407Notes

Reaction equation

HRID 931407 reaction equation
[CH3:1][C@@:2]1([OH:18])[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]1=[O:12].C[Si](Cl)(C)C.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([C:32](Cl)([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:28][CH:27]=1.C([O-])(O)=O.[Na+].[NH4+].[F-]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[OH:18][C@:2]1([CH3:1])[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14]([NH:15][C:32]([C:29]2[CH:28]=[CH:27][C:26]([O:25][CH3:24])=[CH:31][CH:30]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[N:13][C:11]1=[O:12]

Participants

8

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 25516Ammonium fluorideHCID 84462p-(Chlorodiphenylmethyl)anisoleHCID 5009022'-C-MethylcytidineHCID 516892Sodium Bicarbonate

Product 1

HCID 118983440HCID 118983440, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

2′-C-Methylcytidine (38.9 mmol) was dissolved in pyridine (270 mL) and the reaction mixture was cooled down to 0° C. TMSCl (233.4 mmol) was added and the mixture was stirred at room temperature during 4 hours. DMAP (38.9 mmol) and mMTrCl (77.25 mmol) were added and the reaction mixture was stirred at 50° C. during 2 days. The reaction was cooled down to room temperature and a saturated solution of NaHCO3 was added slowly. The mixture was extracted with CH2Cl2 and the organic layer was dried over Na2SO4, filtered and concentrated. Co-evaporations with toluene and CH2Cl2 were done. The crude was dissolved in CH3OH (500 mL) and NH4F (194.5 mmol) was added. The reaction mixture was heated at reflux and stirred during 1 hour. The reaction mixture was cooled down to room temperature and concentrated. The crude was purified by chromatography on a silica gel column (eluent: CH2Cl2/CH3OH 0 to 10%) to give the expected compound as a yellow powder in 89% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 1.08 (s, 3H), 3.71-3.84 (m, 2H), 3.81 (s, 3H), 3.90-3.94 (m, 1H), 3.99-4.03 (m, 1H), 5.14 (d, J=7.63 Hz, 1H), 5.31 (s, 1H), 5.79 (brs, 1H), 6.84 (d, J=8.65 Hz, 2H), 7.13 (d, J=8.69 Hz, 2H), 7.21 (d, J=7.35 Hz, 4H), 7.27-7.34 (m, 8H), 7.51 (brs, 1H).

Workup

  1. stirringthe reaction mixture was stirred at 50° C. during 2 days
  2. temperatureThe reaction was cooled down to room temperature
  3. extractionThe mixture was extracted with CH2Cl2
  4. dry with materialthe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude was dissolved in CH3OH (500 mL)
  8. temperatureThe reaction mixture was heated
  9. temperatureat reflux
  10. stirringstirred during 1 hour
  11. temperatureThe reaction mixture was cooled down to room temperature
  12. concentrationconcentrated
  13. customThe crude was purified by chromatography on a silica gel column (eluent: CH2Cl2/CH3OH 0 to 10%)

Sources & evidence

ORD record
ord-8dfe808dcd6b468bb32726283beea558
Source dataset
uspto-grants-2016_03
Patent number
US09296778B2

Reaction notes

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