Pyridine → 5'-O-[2-(2-nitrophenyl)propyl-sulfonyl]-thymidine

HRID 1859221Notes

Reaction equation

HRID 1859221 reaction equation
[C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.N1C=CC=CC=1.[N+:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH:33]([CH3:39])[CH2:34][S:35](Cl)(=[O:37])=[O:36])([O-:26])=[O:25]>C(Cl)Cl.O>[N+:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH:33]([CH3:39])[CH2:34][S:35]([O:7][CH2:6][C@H:5]1[O:8][C@@H:1]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:2][C@@H:3]1[OH:4])(=[O:37])=[O:36])([O-:26])=[O:25]

Participants

6

Reactant 3

HCID 1049Pyridine2×HCID 5789ThymidineHCID 153824922-(2-Nitrophenyl)propylsulfonyl chloride

Product 1

HCID 153824935'-O-[2-(2-nitrophenyl)propyl-sulfonyl]-thymidineYield 62.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-15 °C

Procedure

242 mg thymidine (1 mmol, co-evaporated 3× each with 5 ml abs. pyridine) are dissolved in 2.5 ml abs. pyridine and cooled to -60° C. 396 mg 2-(2-nitrophenyl)propylsulfonyl chloride (1.5 mmol) in 2.5 ml abs. CH2Cl2 are added drop-wise to this within 10 Min. After stirring 4 h at a temperature between -60 and -30° C., the temperature is allowed to increase to -15° C. After a total of 61/4 h, the reaction is mixed with 15 ml H2O and CH2Cl2 respectively and the aqueous phase is extracted 4× each with 15 ml CH2Cl2. The combined organic phases are dried over Na2SO4, filtered and rotary evaporated. This is co-evaporated 3× with toluene and 1× with methanol. The crude product (600 mg) is purified over flash chromatography (39 g silica gel, 3×11 cm, Sol.: CH2Cl2 /MeOH, cond.: CH2Cl2, gradient: 100 ml CH2Cl2, each 150 ml 100:1, 100:2, 100:3 and 100:4). 290 mg (0.62 mmol, 62%) 5'-O-[2-(2-nitrophenyl)propyl-sulfonyl]-thymidine are obtained as a colorless foam. The obtained mixed fractions are purified by a further column (4.5 g silica gel, 1×11 cm, Sol.: CH2Cl2 /MeOH, cond.: CH2Cl2, gradient: 100 ml CH2Cl2, each 50 ml 100:0.5, 100:1 and 100:2). 128 mg (0.18 mmol, 18%) 3',5'-Di-O-[2-(2-nitrophenyl)-propylsulfonyl]-thymidine are isolated as a colorless foam and 26 mg (0.06 mmol, 6%) 3 '-O-[2 -(2-nitrophenyl)-propylsulfonyl]-thymidine as a light red foam.

Workup

  1. extractionthe aqueous phase is extracted 4× each with 15 ml CH2Cl2
  2. dry with materialThe combined organic phases are dried over Na2SO4
  3. filtrationfiltered
  4. customThe crude product (600 mg) is purified over flash chromatography (39 g silica gel, 3×11 cm, Sol.

Sources & evidence

ORD record
ord-9ebd2dabf129453f91469fb9dca7fe47
Source dataset
uspto-grants-2000_11
Patent number
US06153744

Reaction notes

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