Dimethyl Sulfoxide → (2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-[3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-tetrahydro-furan-2-carbaldehyde

HRID 25677

Reaction equation

HRID 25677 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[Si:11]([O:18][C@@H:19]1[C@H:23]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[C@@H:22]([CH2:32][OH:33])[O:21][C@H:20]1[N:34]1[CH:39]=[CH:38][C:37](=[O:40])[N:36]([CH2:41][C:42]2[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=2)[C:35]1=[O:50])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].C(N(CC)CC)C>C(Cl)Cl.C(OCC)(=O)C>[Si:25]([O:24][C@H:23]1[C@@H:19]([O:18][Si:11]([C:14]([CH3:16])([CH3:15])[CH3:17])([CH3:12])[CH3:13])[C@H:20]([N:34]2[CH:39]=[CH:38][C:37](=[O:40])[N:36]([CH2:41][C:42]3[CH:43]=[CH:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=3)[C:35]2=[O:50])[O:21][C@H:22]1[CH:32]=[O:33])([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 151026051-[(2R,3R,4R,5R)-3,4-bis{[tert-Butyl(dimethyl)silyl]oxy}-5-(hydroxymethyl)tetrahydro-2-furanyl]-3-(4-methoxybenzyl)-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 86587931(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-[3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-tetrahydro-furan-2-carbaldehydeYield 95.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

Following the literature procedure (Myers, A. G.; Gin, D. Y.; Rogers, D. H., J. Amer. Chem. Soc., 1994, 116, 4697-4718), anhydrous dimethyl sulfoxide (3.35 ml, 47.23 mmole) was added dropwise to a solution of oxalyl chloride (14.2 ml, 28.34 mmole, 2.0 M solution in methylene chloride, Aldrich) in anhydrous methylene chloride (50 ml) under argon at −78° C. The resulting mixture was stirred at −78° C. for 45 min, and was transferred via cannula to a cooled (−78° C.) solution of 1-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(hydroxymethyl)tetrahydro-2-furanyl]-3-(4-methoxybenzyl)-2,4(1H,3H)-pyrimidinedione (5.6 g, 9.45 mmole, obtained from Reference Example 2) in anhydrous methylene chloride (50 ml) under argon. The resulting mixture was stirred at −78° C. for 1 h, and triethylamine (9.9 ml, 70.8 mmole) was added all at once. The mixture was stirred at −78° C. for 1.5 h under argon, and diluted with ethyl acetate (500 ml). The organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. Toluene was added to the residue, and evaporated in vacuo. This procedure was repeated for two more times, to give 1-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-[3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-tetrahydro-furan-2-carbaldehyde as pale yellow solid (5.31 g, 95%). This material was used in its crude form in the following experiment. MS (ES): m/z 591.3 (M+H).

Workup

  1. stirringThe resulting mixture was stirred at −78° C. for 1 h
  2. stirringThe mixture was stirred at −78° C. for 1.5 h under argon
  3. washThe organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness in vacuo
  7. additionToluene was added to the residue
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-803d2059deb34c5c9b6870ade81406d3
Source dataset
uspto-grants-2005_02
Patent number
US06858591B2

Linked notes

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