Methanol → HCID 46844020, compound

HRID 1920694Notes

Reaction equation

HRID 1920694 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.[CH3:38][OH:39].C[O-].[Na+]>C(O)(=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:39][CH3:38])[N:21]=1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 10942334Sodium MethoxideHCID 533058126-Chloro-9-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-2-methyl-beta-D-ribofuranosyl)-9H-purin-2-amine

Product 1

HCID 46844020HCID 46844020, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a 250 mL dry round-bottomed flask was charged (2R,3R,4R,5R)-5-(2-amino-6-chloro-9H-purin-9-yl)-2-(benzoyloxymethyl)-4-fluoro-4-methyltetrahydrofuran-3-yl benzoate (12, 7.50 g, 14.26 mmol) Anhydrous methanol (30 mL) was added and a white suspension was formed. At 50° C., a solution of sodium methoxide in methanol (25%, 19.7 mL, 64.17 mmol) was added via a dry syringe under a nitrogen atmosphere. A white cloudy reaction mixture was formed. After 3.5 h at 50° C., the reaction was complete with no starting material left as shown by TLC test. The mixture was cooled down to room temperature and neutralized by addition of glacial acetic acid (3 mL). A white solid was filtered out and washed with methanol (3×5 mL). The filtrate was mixed with 20 g of silica gel and concentrated to dryness. The mixture was loaded in line with a silica gel cartridge and separated via column chromatography using a gradient of methanol in dichloromethane 0 to 15% MeOH. The product eluted out at 12% methanol in dichloromethane. The product containing fractions were combined, concentrated under reduced pressure and dried under vacuum (0.2 mmHg, 50° C., 24 h) to a white powder solid (4.45 g, 98% yield), mp 199-202° C.

Workup

  1. additionwas added
  2. customa white suspension was formed
  3. customA white cloudy reaction mixture
  4. customwas formed
  5. waitleft
  6. filtrationA white solid was filtered out
  7. washwashed with methanol (3×5 mL)
  8. additionThe filtrate was mixed with 20 g of silica gel
  9. concentrationconcentrated to dryness
  10. customseparated via column chromatography
  11. washThe product eluted out at 12% methanol in dichloromethane
  12. additionThe product containing fractions
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2e193e3edd6b4f14a0065982453886be
Source dataset
uspto-grants-2012_05
Patent number
US08173621B2

Reaction notes

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