Thymine → (2R,5R)-5-t-butoxycarbonyloxymethyl-5-ethynyl-2-(thymin-1-yl)-2,5-dihydrofuran

HRID 1503307Notes

Reaction equation

HRID 1503307 reaction equation
[NH:1]1[CH:9]=[C:7]([CH3:8])[C:5](=[O:6])[NH:4][C:2]1=[O:3].[C:10]([O:14][C:15]([O:17][CH2:18][C@@:19]1([C:32]#[CH:33])[O:23][C@@H:22](OC(OC(C)(C)C)=O)[CH:21]=[CH:20]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:10]([O:14][C:15]([O:17][CH2:18][C@@:19]1([C:32]#[CH:33])[O:23][C@@H:22]([N:1]2[CH:9]=[C:7]([CH3:8])[C:5](=[O:6])[NH:4][C:2]2=[O:3])[CH:21]=[CH:20]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 2

HCID 1135ThymineHCID 53372554(2S,5R)-5-t-butoxycarbonyloxymethyl-5-ethynyl-2-t-butoxycarbonyloxy-2,5-dihydrofuran

Product 1

HCID 53372555(2R,5R)-5-t-butoxycarbonyloxymethyl-5-ethynyl-2-(thymin-1-yl)-2,5-dihydrofuranYield 72%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
55 °C

Procedure

Thymine (16.7 g), N,N′-dimethylformamide (162 g), and tetrakis(triphenylphosphine)palladium(0) (917 mg) were added to a glass reactor under nitrogen, and the mixture was heated to 55° C. Then, a solution of (2S,5R)-5-t-butoxycarbonyloxymethyl-5-ethynyl-2-t-butoxycarbonyloxy-2,5-dihydrofuran (β/α=>99/1) (9.0 g) in N,N′-dimethylformamide was added dropwise thereto, and the mixture was stirred for 30 minutes. The reaction mixture was filtered, and water was added to the filtrate, followed by stirring for phase separation. The thus-separated organic layer was concentrated. The residue was purified through recrystallization from acetonitrile and toluene, to thereby yield 6.5 g of (2R,5R)-5-t-butoxycarbonyloxymethyl-5-ethynyl-2-(thymin-1-yl)-2,5-dihydrofuran (yield: 72%, β/α=>99/1). The 1H-NMR data of the compound are as follows.

Workup

  1. filtrationThe reaction mixture was filtered
  2. additionwater was added to the filtrate
  3. stirringby stirring for phase separation
  4. concentrationThe thus-separated organic layer was concentrated
  5. customThe residue was purified through recrystallization from acetonitrile and toluene

Sources & evidence

ORD record
ord-df253cb17a4d492dbb6df74ec33400d0
Source dataset
uspto-grants-2015_12
Patent number
US09212174B2

Reaction notes

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