Sodium Hydroxide → Thymidine, 3'-deoxy-3'-[(triphenylmethyl)amino]-

HRID 342915Notes

Reaction equation

HRID 342915 reaction equation
[C:1]([NH:20][C@@H:21]1[C@@H:25]([CH:26](C(=O)C2C=CC(OC)=CC=2)[OH:27])[O:24][C@@H:23]([N:38]2[CH:46]=[C:44]([CH3:45])[C:42](=[O:43])[NH:41][C:39]2=[O:40])[CH2:22]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>O1CCOCC1.CO>[C:1]([NH:20][C@@H:21]1[C@@H:25]([CH2:26][OH:27])[O:24][C@@H:23]([N:38]2[CH:46]=[C:44]([CH3:45])[C:42](=[O:43])[NH:41][C:39]2=[O:40])[CH2:22]1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 701174643'-(Trityl)amino-5'-(4-methoxybenzoyl)-3'-deoxythymidine

Product 1

HCID 11670250Thymidine, 3'-deoxy-3'-[(triphenylmethyl)amino]-Yield 90%

Reagents, catalysts & solvents 1

HCID 21966525Dioxane MethanolSolvent

Procedure

The 5'-O-anisoyl protecting group was removed by dissolving 2t (30.1 g, 48.7 mmol) in 57:43 1,4-dioxane/MeOH (150 mL), followed by the addition of 2M aq. NaOH (73.1 mL, 146.2 mmol). After stirring for 1.5 h at ambient temperature, the reaction mixture was neutralized with Dowex 50W-X8 cation exchange resin (ca. 150 g of dry pyridinium H+ -form, 1.6 meq/g). Once the pH was neutral (ca. 10 min), the resin was filtered, washed extensively with CH2Cl2 and MeOH, and the crude product was concentrated in vacuo. The residue was redissolved in EtOAc (500 mL) and extracted with saturated. aq. NaHCO3 (2×250 mL), H2O (250 mL), and saturated. aq. NaCl (250 mL). After drying over Na2SO4 and filtration, the solvents were removed in vacuo, and the resulting foam was redissolved in 95:5 CH2Cl2 /MeOH (300 mL). This solution was added slowly to a rapidly stirring mixture of 1:1 Et2O/hexane (1250 mL) to precipitate the pure 3'-(Trityl)amino-3'-deoxythymidine, 3t, in 90% yield (21.2 g, 43.8 mmol). Conversion to phosphoramidite monomers and/or succinylated nucleoside is described in Examples 5-7 below.

Workup

  1. customThe 5'-O-anisoyl protecting group was removed
  2. custom(ca. 10 min)
  3. filtrationthe resin was filtered
  4. washwashed extensively with CH2Cl2 and MeOH
  5. concentrationthe crude product was concentrated in vacuo
  6. dissolutionThe residue was redissolved in EtOAc (500 mL)
  7. extractionextracted with saturated
  8. dry with materialAfter drying over Na2SO4 and filtration
  9. customthe solvents were removed in vacuo
  10. dissolutionthe resulting foam was redissolved in 95:5 CH2Cl2 /MeOH (300 mL)
  11. additionThis solution was added slowly to
  12. stirringa rapidly stirring
  13. additionmixture of 1:1 Et2O/hexane (1250 mL)
  14. customto precipitate the pure 3'-(Trityl)amino-3'-deoxythymidine, 3t

Sources & evidence

ORD record
ord-9add01400b0449f998d4b0d4d4c98a88
Source dataset
uspto-grants-1999_01
Patent number
US05859233

Reaction notes

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