Chlorotrimethylsilane → n6-Benzoyl-8-bromo-5'-o-(4,4'-dimethoxytrityl)-2'-deoxyadenosine

HRID 500294Notes

Reaction equation

HRID 500294 reaction equation
[Br:1][C:2]1[N:3]([C:12]2[N:13]=[CH:14][N:15]=[C:16]([NH2:19])[C:17]=2[N:18]=1)[C@@H:4]1[O:11][C@H:8]([CH2:9][OH:10])[C@@H:6]([OH:7])[CH2:5]1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28](Cl)([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:24][CH:23]=1.C[Si](C)(C)Cl.[C:49](Cl)(=[O:56])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>N1C=CC=CC=1>[C:49]([NH:19][C:16]1[C:17]2[N:18]=[C:2]([Br:1])[N:3]([C:12]=2[N:13]=[CH:14][N:15]=1)[C@@H:4]1[O:11][C@H:8]([CH2:9][O:10][C:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C:25]2[CH:26]=[CH:27][C:22]([O:21][CH3:20])=[CH:23][CH:24]=2)[C@@H:6]([OH:7])[CH2:5]1)(=[O:56])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 7412Benzoyl chlorideHCID 965478-Bromo-2'-deoxyadenosineHCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)2×

Product 1

HCID 14656959n6-Benzoyl-8-bromo-5'-o-(4,4'-dimethoxytrityl)-2'-deoxyadenosineYield 41.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

8-Bromo-2′-Deoxyadenosine (7.7 gm. 22.17 mmol) was dried by co-evaporation with dry pyridine and the solid was suspended in 200 ml of dry pyridine followed by the addition of 4,4′-dimethoxytriphenylmethyl chloride (DMT-Cl) (9 gm, 26.6 mmol). After stirring for 4 hrs at RT, TLC on silica gel showed that a new product was formed and some starting material was unreacted. Another amount of DMT-Cl (3 gm) was added and stirred at RT for 2 hrs. When TLC showed that all starting material was converted to new product with higher Rf, the reaction mixture was cooled to 0 C and trimethylchlorosilane (12.042 gm., 14 ml, 110.85 mmol) was added dropwise while cooling and after 40 min. while stirring benzoyl chloride (15.58 gm, 12.88 ml, 110.85 mmol) was similarly added. The reaction was allowed to react at RT over 2 hrs. The reaction was quenched by slow addition of cold water (50 ml), followed by addition of concentrated ammonia (30%, 50 ml). After 30 min. the reaction mixture was evaporated to dryness. The residue was dissolved in water, and the solution was extracted with ethyl acetate three times, the organic layer washed with saturated sodium bicarbonate solution, and then brine. The organic phase was dried over sodium sulphate, evaporated to dryness. The product was purified on a silica column chromatography, to give a yellowish solid product (6.79 gm, 41.6%). The structure of this product was confirmed by H NMR and ES-MS.

Workup

  1. customwas formed
  2. stirringstirred at RT for 2 hrs
  3. additionwas added dropwise
  4. temperaturewhile cooling and after 40 min.
  5. additionwas similarly added
  6. customto react at RT over 2 hrs
  7. customThe reaction was quenched by slow addition of cold water (50 ml)
  8. additionfollowed by addition of concentrated ammonia (30%, 50 ml)
  9. customAfter 30 min. the reaction mixture was evaporated to dryness
  10. dissolutionThe residue was dissolved in water
  11. extractionthe solution was extracted with ethyl acetate three times
  12. washthe organic layer washed with saturated sodium bicarbonate solution
  13. dry with materialThe organic phase was dried over sodium sulphate
  14. customevaporated to dryness
  15. customThe product was purified on a silica column chromatography

Sources & evidence

ORD record
ord-14250d84bda74255a456710d742ce740
Source dataset
uspto-grants-2010_08
Patent number
US07771929B2

Reaction notes

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