Acetic Acid → Thymidine

HRID 2184168Notes

Reaction equation

HRID 2184168 reaction equation
C([C@@H:3]1[C@@H:7]([CH2:8][O:9]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[O:6][C@@H:5]([N:29]2[CH:37]=[C:35]([CH3:36])[C:33](=[O:34])[NH:32][C:30]2=[O:31])[CH2:4]1)=O.CC(O)=[O:40].Cl.CON>C(Cl)Cl.CO>[C@@H:5]1([N:29]2[CH:37]=[C:35]([CH3:36])[C:33](=[O:34])[NH:32][C:30]2=[O:31])[O:6][C@H:7]([CH2:8][OH:9])[C@@H:3]([OH:40])[CH2:4]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 521874O-Methylhydroxylamine hydrochlorideHCID 15747240HCID 15747240, compound

Product 1

HCID 5789Thymidine

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

To a stirred solution of 3′-deoxy-3′-C-formyl-5′-O-tritylthymidine (0.59, 1 mmol, prepared as per Example 4 in CH2Cl2:MeOH (2:1, 30 vol.) was added AcOH (0.5 ml) and methoxyamine hydrochloride (0.189, 2.2 mml) at room temperature. The mixture was stirred for 30 min., concentrated under vacuum and the residue dissolved in MeOH (20 ml). To this solution, concentrated HCl (0.1 ml) was added and stirred for 1 h. The solution was neutralized with NH4OH (≈2 ml) and concentrated under a vacuum to furnish the 3′-C-[(methoxyimido)methyl] derivative of thymidine. 1H NMR (CDCl3) δ 9.67 (s, 1, NH); 7.67 (s, 1, H-6); 7.33 (d, 0.70, H-3″ E isomer), 6.65 (d, 0.30, H-3′ Z isomer); 6.15 (m, 1, H-1′); 3.60-4.12 (m, 3.3, H-4′, H-5′5″, H-3′ Z isomer); 3.91 (s, 0.9, OCH3 Z isomer); 3.82 (s, 2.1, OCH3 oxime E isomer); 3.26 (m, 0.7, H-3′ E isomer); 2.27-2.60 (m, 2, H-2′,2″); 1.91 (2s, 3, C6CH3).

Workup

  1. concentrationconcentrated under vacuum
  2. dissolutionthe residue dissolved in MeOH (20 ml)
  3. additionTo this solution, concentrated HCl (0.1 ml) was added
  4. stirringstirred for 1 h
  5. concentrationconcentrated under a vacuum

Sources & evidence

ORD record
ord-fde36edd8f194cb4a2c0b2007a8a27c5
Source dataset
uspto-grants-2005_05
Patent number
US06900301B2

Reaction notes

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