Acetic Acid → 1-(3-O-Acetyl-2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl)-thymine

HRID 2274451Notes

Reaction equation

HRID 2274451 reaction equation
[C:1]([O:4][C@H:5]1[C@@H:9]([CH2:10]I)[O:8][C@@H:7]([N:12]2[CH:20]=[C:18]([CH3:19])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)(=[O:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(O)=O.N(C(OCC)=O)=NC(OCC)=O.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CO>[C:1]([O:4][C@H:5]1[C:9](=[CH2:10])[O:8][C@H:7]([N:12]2[CH:20]=[C:18]([CH3:19])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)(=[O:3])[CH3:2]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 121116121-(3-O-acetyl-2,5-dideoxy-5-iodo-beta-D-threopentofuranosyl)thymine

Product 1

HCID 670245471-(3-O-Acetyl-2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl)-thymineYield 127.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 7 (1.08 g, 2.63 mmol), Ph3P (897 mg, 3.42 mmol) and AcOH (301 μL, 5.26 mmol) in THF (10 mL) was cooled to 0 under positive pressure of dry Ar. To this was added dropwise diethyl azodicarboxylate (2.3 M solution in toluene, 1.49 mL, 3.42 mol). After stirring for 30 min, the mixture was partitioned between CH2Cl2 and sat. aqueous NaHCO3. The organic layer was dried (Na2SO4) and evaporated. The residue was treated with K2CO3 (727 mg, 5.26 mmol) in MeOH (5 mL) for 1 h. The mixture was partitioned between CHCl3 and brine. The organic layer was dried (Na2SO4), evaporated, and chromatographed on a silica gel column (hexane/EtOAc=4/1). This gave 8 (892 mg, 83%) as an oil.

Workup

  1. temperaturewas cooled to 0 under positive pressure of dry Ar
  2. customthe mixture was partitioned between CH2Cl2 and sat. aqueous NaHCO3
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. customevaporated
  5. customThe mixture was partitioned between CHCl3 and brine
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. customevaporated
  8. customchromatographed on a silica gel column (hexane/EtOAc=4/1)

Sources & evidence

ORD record
ord-2ef2f58ed82840e284e34cd4486fd4fb
Source dataset
uspto-grants-2015_09
Patent number
US09126971B2

Reaction notes

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