Thymidine → 5'-O-phthalimidothymidine

HRID 2395834Notes

Reaction equation

HRID 2395834 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.O[N:19]1[C:23](=[O:24])[C:22]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]2[C:20]1=[O:29].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>CN(C=O)C>[C:23]1(=[O:24])[N:19]([O:7][CH2:6][C@H:5]2[O:8][C@@H:1]([N:9]3[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]3=[O:11])[CH2:2][C@@H:3]2[OH:4])[C:20](=[O:29])[C:21]2=[CH:28][CH:27]=[CH:26][CH:25]=[C:22]12

Participants

6

Reactant 4

HCID 5789ThymidineHCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 157472435'-O-phthalimidothymidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of thymidine (24.22 g, 0.1 mol), N-hydroxyphthalimide (21.75 g, 0.13 mol), triphenylphosphine (34 g, 0.13 mol) in dry DMF (400 ml) was added diisopropylazodicarboxylate (30 ml, 0.15 mol) over a period of 3 h at 0° C. After complete addition the reaction mixture was warmed up to room temperature and stirred for 12 h. The solution was concentrated under vacuum (0.1 mm, <40° C.) to furnish an orange-red residue. The residual gum was washed several times with Et2O and washing were discarded. The semi-solid residue was suspended in EtOH (500 ml) and heated (90° C.) to dissolve the product. On cooling 30.98 g (80%) of 5'-O-phthalimidothymidine was collected in 3-crops as white crystalline material, mp 233°-235° C. (decomp.); 1H NMR (DMSO-d6) δ11.29 (s, 1, NH), 7.85 (m , 4, ArH), 7.58 (s, 1, C6H), 6.20 (t, 1, H1', J1',2' =7.8 Hz, J1',2" =6.5 Hz ), 5.48 (d, 1, OH3'), 4.36 (m, 3, H4',5',5"), 4.08 (m, 1, H3'), 2.09-2.13 (m, 2, H2',2"), and 1.79 (s, 3, CH3). Anal. Calcd. for C18H17O7N3. 0.7 H2O: C, 54.05; H, 4.64; N, 10.51. Found: C, 53.81; H, 4.25; N, 10.39.

Workup

  1. additionAfter complete addition the reaction mixture
  2. concentrationThe solution was concentrated under vacuum (0.1 mm, <40° C.)
  3. customto furnish an orange-red residue
  4. washThe residual gum was washed several times with Et2O
  5. washwashing
  6. temperatureheated (90° C.)
  7. dissolutionto dissolve the product
  8. temperatureOn cooling 30.98 g (80%) of 5'-O-phthalimidothymidine
  9. customwas collected in 3-crops as white crystalline material, mp 233°-235° C. (decomp.)

Sources & evidence

ORD record
ord-a37570e80cb8455ab5f433212bb0a87a
Source dataset
uspto-grants-1996_02
Patent number
US05489677

Reaction notes

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