Imidazole → HCID 66802642, compound

HRID 515935Notes

Reaction equation

HRID 515935 reaction equation
[F:1][C@:2]1([CH3:18])[C@H:6]([OH:7])[C@@H:5]([CH2:8]O)[O:4][C@H:3]1[N:10]1[CH:15]=[CH:14][C:13](=[O:16])[NH:12][C:11]1=[O:17].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N1C=CN=C1.[I:43]I>C1COCC1>[F:1][C@:2]1([CH3:18])[C@H:6]([OH:7])[C@@H:5]([CH2:8][I:43])[O:4][C@H:3]1[N:10]1[CH:15]=[CH:14][C:13](=[O:16])[NH:12][C:11]1=[O:17]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 113115032'-Deoxy-2'-fluoro-2'-methyluridine

Product 1

HCID 66802642HCID 66802642, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

Chiral 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidine-2,4-dione (6.14 g, 23.6 mmol), PPh3 (9 g, 34.4 mmol), imidazole (2.4 g, 34.4 mmol) and dry THF (100 mL) were added into a 3-neck flask bottle (500 mL), the mixture was stirred at 20° C. under nitrogen atmosphere for 20 min. Then I2 (6.6 g, 26 mmol) dissolved in dry THF (100 mL) was added into the mixture dropwise at 20° C. during 30 min, after addition, the whole mixture was stirred at 20° C. under nitrogen atmosphere for 18 hrs. TLC showed that the SM was consumed, then water (50 mL) was added into it, the mixture was extracted by EA (150 mL×3), organic layer was washed with brine, dried over Na2SO4, removed solvent by reduced pressure, residue was purified by silica gel chromatography column (DCM:MeOH=100:1 to 50:1) to afford the title compound as a white solid (8.2 g, 94%).

Workup

  1. additionwas added into the mixture dropwise at 20° C. during 30 min
  2. additionafter addition
  3. stirringthe whole mixture was stirred at 20° C. under nitrogen atmosphere for 18 hrs
  4. customwas consumed
  5. additionwater (50 mL) was added into it
  6. extractionthe mixture was extracted by EA (150 mL×3), organic layer
  7. washwas washed with brine
  8. dry with materialdried over Na2SO4
  9. customremoved solvent by reduced pressure, residue
  10. customwas purified by silica gel chromatography column (DCM:MeOH=100:1 to 50:1)

Sources & evidence

ORD record
ord-3195089ff26a44eb95669b754bd2de8d
Source dataset
uspto-grants-2015_08
Patent number
US09108999B2

Reaction notes

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