Acetic Anhydride → 5'-O-Benzoyl-2',3'-didehydro-3'-deoxy-4'-ethynylthymidine

HRID 2274450Notes

Reaction equation

HRID 2274450 reaction equation
[BH4-].[Na+].[C:3]([O:11][CH2:12][C@@:13]1([C:32]#[CH:33])[O:17][C@@H:16]([N:18]2[CH:26]=[C:24]([CH3:25])[C:22](=[O:23])[NH:21][C:19]2=[O:20])[CH2:15][C@H:14]1OS(C)(=O)=O)(=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CCN(C(C)C)C(C)C.CC(OC(C)=O)=O>C1COCC1.CO.CN(C1C=CN=CC=1)C.CO>[C:3]([O:11][CH2:12][C@@:13]1([C:32]#[CH:33])[O:17][C@@H:16]([N:18]2[CH:26]=[C:24]([CH3:25])[C:22](=[O:23])[NH:21][C:19]2=[O:20])[CH:15]=[CH:14]1)(=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 866392191-[5-O-Benzoyl-2-deoxy-4-ethynyl-3-O-methanesulfonyl-beta-D-threo-pentofuranosyl]thymine

Product 1

HCID 722046195'-O-Benzoyl-2',3'-didehydro-3'-deoxy-4'-ethynylthymidineYield 127.9%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

A mixture of NaBH4 (628 mg, 16.6 mmol) and MeOH (50 ml) was cooled and stirred at −70° C. To this was added a mixture of 5 (3.39 g, 8.3 mmol) and CeCl3.7H2O (3.1 g, 8.3 mmol) in THF/MeOH=1/1 (50 ml) dropwise over 15 min. The resulting suspension was stirred for 1 h at the −70□. The reaction was quenched by adding AcOH (ca. 1 mL). The reaction mixture was evaporated. The residue was suspended in MeCN (15 ml). To this suspension were added DMAP (1.02 g, 8.3 mmol), i-Pr2NEt (1.45 mL, 8.3 mmol) and Ac2O (1.57 mL, 16.6 mmol). The mixture was stirred for 30 min at 0° under positive pressure of dry Ar, and partitioned between CH2Cl2 and sat. aqueous NaHCO3. The organic layer was dried (Na2SO4), evaporated, and chromatographed on a silica gel column (hexane/EtOAc=4/1). This gave 6 (3.74 g, 100%) as an oil.

Workup

  1. temperaturewas cooled
  2. additionTo this was added
  3. stirringThe resulting suspension was stirred for 1 h at the −70□
  4. customThe reaction was quenched
  5. additionby adding AcOH (ca. 1 mL)
  6. customThe reaction mixture was evaporated
  7. stirringThe mixture was stirred for 30 min at 0° under positive pressure of dry Ar
  8. custompartitioned between CH2Cl2 and sat. aqueous NaHCO3
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. customevaporated
  11. customchromatographed on a silica gel column (hexane/EtOAc=4/1)

Sources & evidence

ORD record
ord-2a0a393d31204ffc8e593f5e952ae75b
Source dataset
uspto-grants-2015_09
Patent number
US09126971B2

Reaction notes

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