Borane → 2'-o-Phthalimidoethyl-5-methyluridine

HRID 1250000Notes

Reaction equation

[OH:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[C:7]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:6]2[C:5]1=[O:14].B.[H][H].[CH3:18][C:19]1[C:33](=[O:34])[N:32]=[C:31]2[N:21]([C@@H:22]3[O:26][C@H:25]([CH2:27][OH:28])[C@@H:24]([OH:29])[C@@H:23]3[O:30]2)[CH:20]=1.C(=O)(O)[O-].[Na+]>O1CCCC1>[C:8]1(=[O:9])[N:4]([CH2:3][CH2:2][O:1][C@@H:23]2[C@H:24]([OH:29])[C@@H:25]([CH2:27][OH:28])[O:26][C@H:22]2[N:21]2[CH:20]=[C:19]([CH3:18])[C:33](=[O:34])[NH:32][C:31]2=[O:30])[C:5](=[O:14])[C:6]2=[CH:13][CH:12]=[CH:11][CH:10]=[C:7]12

Participants

Conditions

Temperature: 150 °C

Procedure

N-(2-Hydroxyethyl)phthalimide (277 g, 1.45 mol) was slowly added to a solution of borane in tetrahydrofuran (1 M, 600 mL) with stirring. Hydrogen gas evolved as the solid dissolved. Once the rate of bubbling subsided, the solution was placed in a 2 L stainless steel bomb. 2,2′-anhydro-5-methyluridine (60 g, 0.25 mol) and sodium bicarbonate (120 mg) were added and the bomb was sealed. After 30 minutes, the bomb was vented for the last time and then placed in an oil bath and heated to 150° C. internal temperature for 24 hours. The bomb was cooled to room temperature and opened. TLC revealed all the starting material was gone. The crude solution was concentrated and the residue was columned on silica gel starting with straight ethyl acetate to remove the excess phthalimide reagent followed by ethyl acetate-methanol 95/5 to elute the product to give 22.2 g (20.6%) of ca 90% pure product.

Workup

dissolutiondissolved
customOnce the rate of bubbling
customthe bomb was sealed
customplaced in an oil bath
temperatureThe bomb was cooled to room temperature
concentrationThe crude solution was concentrated
customto remove the excess phthalimide reagent
washto elute the product

Sources & evidence

ORD record: ord-d9c4b76605064fd0b929d8fdbe98ba41
Source dataset: uspto-grants-2002_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06335437B1

Reaction notes

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