Benzenesulfonic Acid → 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

HRID 25676

Reaction equation

[H-].[Na+].COC1C=CC(C(C2C=CC(OC)=CC=2)[O:12][CH:13](C2C=CC=CC=2)[CH:14]2[O:18][CH:17]([N:19]3[CH:24]=[CH:23][C:22](=[O:25])[NH:21][C:20]3=[O:26])[CH:16]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH:15]2[O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])=CC=1.[CH3:57][O:58][C:59]1[CH:66]=[CH:65][C:62]([CH2:63]Cl)=[CH:61][CH:60]=1.C1(S(O)(=O)=O)C=CC=CC=1>CN(C)C=O.C(OCC)(=O)C>[Si:28]([O:27][C@@H:16]1[C@H:15]([O:35][Si:36]([C:39]([CH3:41])([CH3:42])[CH3:40])([CH3:37])[CH3:38])[C@@H:14]([CH2:13][OH:12])[O:18][C@H:17]1[N:19]1[CH:24]=[CH:23][C:22](=[O:25])[N:21]([CH2:63][C:62]2[CH:65]=[CH:66][C:59]([O:58][CH3:57])=[CH:60][CH:61]=2)[C:20]1=[O:26])([C:31]([CH3:33])([CH3:34])[CH3:32])([CH3:30])[CH3:29]

Participants

Conditions

Temperature: 0 °C

Procedure

Following the procedure (Myers, A. G.; Gin, D. Y.; Rogers, D. H., J. Amer. Chem. Soc., 1994, 116, 4697-4718), a suspension of sodium hydride (1.55 g, 38.75 mmole, 60% oil dispersion) in anhydrous dimethylformamide (40 ml) was cooled at 0° C. under argon, and to this mixture was added a solution of 1-[5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3,4-bis-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-furan-2-yl]-1H-pyrimidine-2,4-dione (20 g, 25.8 mmole, obtained from Reference Example 1) in anhydrous dimethylformamide (35 ml) over a period of 15 min. Neat p-methoxybenzyl chloride (7 ml, 51 mmole) was added to this solution. The resulting mixture was stirred at 0° C. for 15 h under argon, and diluted with ethyl acetate (700 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. The oily residue was dissolved in chloroform (200 ml) and cooled at 0° C. under nitrogen. Benzenesulfonic acid (6 g, 37.93 mmole) was added portionwise, and the resulting red solution was stirred at 0° C. under nitrogen for 2 h. The mixture was diluted with ethyl acetate. 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. The residue was chromatographed (flash column, silica gel, methylene chloride:diethyl ether:methanol=95:3:2) to give 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 as white solid (9 g, 59%).

Workup

washThe organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated to dryness in vacuo
dissolutionThe oily residue was dissolved in chloroform (200 ml)
temperaturecooled at 0° C. under nitrogen
stirringthe resulting red solution was stirred at 0° C. under nitrogen for 2 h
washThe organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated sodium chloride solution
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated to dryness in vacuo
customThe residue was chromatographed (flash column, silica gel, methylene chloride:diethyl ether:methanol=95:3:2)

Sources & evidence

ORD record: ord-59f28981d8944a63b3f8938c9a99b206
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06858591B2

Linked notes

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