Benzyl Alcohol → HCID 46843957, compound

HRID 1019526Notes

Reaction equation

HRID 1019526 reaction equation
C([O:9][C@H:10]1[C@:14]([F:16])([CH3:15])[C@H:13]([N:17]2[CH:25]=[N:24][C:23]3[C:18]2=[N:19][C:20]([NH2:27])=[N:21][C:22]=3Cl)[O:12][C@@H:11]1[CH2:28][O:29]C(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[CH2:38]([OH:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[H-].[Na+].Cl>CN(C=O)C>[NH2:27][C:20]1[N:19]=[C:18]2[C:23]([N:24]=[CH:25][N:17]2[C@@H:13]2[O:12][C@H:11]([CH2:28][OH:29])[C@@H:10]([OH:9])[C@:14]2([F:16])[CH3:15])=[C:22]([O:45][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:21]=1

Participants

6

Reactant 4

HCID 244Benzyl Alcohol2×HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 533058126-Chloro-9-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-2-methyl-beta-D-ribofuranosyl)-9H-purin-2-amine

Product 1

HCID 46843957HCID 46843957, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a 500 mL of dry round-bottomed flask were added (2R,3R,4R,5R)-5-(2-amino-6-chloro-9H-purin-9-yl)-2-(benzoyloxymethyl)-4-fluoro-4-methyltetrahydrofuran-3-yl benzoate (6, 8.0 g, 15.2 mmol) and anhydrous benzyl alcohol (128 mL). To another 250 mL of dry round-bottomed flask were charged NaH (60% in mineral oil, 2.44 g, 60.8 mmol) and anhydrous DMF (40 mL). The suspension was stirred at 0° C. in an ice-water bath. Benzyl alcohol (27 mL) was added drop-wise via a syringe. A solution was slowly formed and it was transferred to the nucleoside suspension quickly under a nitrogen atmosphere at room temperature. The mixture was heated to 50° C. and stirred. The reaction was complete after 3 h and cooled to ambient temperature. It was neutralized by the addition of 4 N HCl to ca. pH=7 (12 mL). The solution was concentrated under reduced pressure (4 mbar, 90° C. bath). The cloudy residue was diluted with dichloromethane (100 mL) and washed with water (3×30 mL), brine (30 mL) and dried over Na2SO4. The suspension was filtered and the filtrate was concentrated under reduced pressure to an oily residue. This was purified by column chromatography (Analogix, 0 to 8% gradient of MeOH in DCM). The product eluted at 4% MeOH in DCM. The product containing fractions were combined, concentrated under reduced pressure and dried (50° C., 0.2 mmHg, 17 h) to a white foam solid (4.57 g, 11.7 mmol, 77.2%).

Workup

  1. customA solution was slowly formed
  2. temperatureThe mixture was heated to 50° C.
  3. stirringstirred
  4. temperaturecooled to ambient temperature
  5. concentrationThe solution was concentrated under reduced pressure (4 mbar, 90° C. bath)
  6. additionThe cloudy residue was diluted with dichloromethane (100 mL)
  7. washwashed with water (3×30 mL), brine (30 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationThe suspension was filtered
  10. concentrationthe filtrate was concentrated under reduced pressure to an oily residue
  11. customThis was purified by column chromatography (Analogix, 0 to 8% gradient of MeOH in DCM)
  12. washThe product eluted at 4% MeOH in DCM
  13. additionThe product containing fractions
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6917f40765b746cc8ecc0f2109afaea7
Source dataset
uspto-grants-2014_05
Patent number
US08716262B2

Reaction notes

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