Imidazole → HCID 22866033, compound

HRID 355458Notes

Reaction equation

HRID 355458 reaction equation
[OH-].[Na+].[Si:3]([O:20][CH2:21][C@H:22](O)[CH2:23][CH2:24][C:25]([OH:27])=[O:26])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.S(OC)(OC)(=O)=O.[Si](OC[C@@H](I)CCC(O)=O)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.II.[C:88]([O-:91])(=[S:90])[CH3:89]>C(O)C.CS(C)=O.C1(C)C=CC=CC=1>[C:88]([S:90][C@@H:22]([CH2:21][O:20][Si:3]([C:16]([CH3:17])([CH3:19])[CH3:18])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH2:23][CH2:24][C:25]([OH:27])=[O:26])(=[O:91])[CH3:89]

Participants

12

Reactant 8

HCID 795ImidazoleHCID 807IodineHCID 6497Dimethyl SulfateHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 22866034HCID 22866034, compoundHCID 22866035HCID 22866035, compound2×HCID 178476994HCID 178476994, compound

Product 1

HCID 22866033HCID 22866033, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

D-glutamic acid (1) was treated with sodium nitrite in hydrochloric acid to produce (R)-1,4-butyrolactone-4-carboxylic acid (2). Compound 2 was then reduced by borane-dimethyl sulfide complex in THF to give the corresponding (R)-4-(hydroxymethyl)-4-butyrolactone (4), which was subsequently treated with tert-butyldiphenylsilyl chloride in methylene chloride using imidazole as a catalyst to afford (R)-5-O-tert-butyldiphenylsilyl-4-hydroxymethyl-1,4-butyrolactone (53). The protected lactone 53 was opened with sodium hydroxide in ethanol and then converted to the methyl ester of 5-[(tert-butyldiphenylsilyl)oxy]-4-(R)-hydroxypentanoic acid (54) by reaction with dimethyl sulfate in dimethyl sulfoxide. Commpound 54 was transformed into the methyl ester of 5-[(tert-butyldiphenylsilyl)oxy]-4-(S)-iodopentanoic acid (55) by treatment with triphenylphosphine, imidazole and iodine. Displacement of the iodo group in compound 55 by thioacetate in toluene occurred readily to give the methyl ester of 4-(R)-(acetylthio)-5-[(tert-butyldiphenylsilyl)oxy]pentanoic acid (56). Compound 56 was then treated with 2 equivalents of diisobutylaluminum hydride (DIBAL) in toluene to reductively deprotect the sulfur and reduce the methyl ester to an aldehyde, thereby producing the thiolactol via spontaneous cyclization. The thiolactol was acetylated with acetic anhydride in pyridine to give 1-o-acetyl-5-o-(tert-butyldiphenylsilyl)-2,3-dideoxy-4-thio-L-ribofuranose (57): 1HNMR (CDCl3) delta 7.67 (m, 4H, ArH), 7.40 (m, 6H, ArH), 6.10 (m, 1H, 1-H), 3.70 (m, 1H, 4-H), 3.52 (m, 2H, 5-H), 2.20 (m, 2H, CH2), 2.00 (2 s, 3H, CH3CO--), 1.92 (m, 2H, CH2), 1.08 (s, 9H, tert-butyl).

Sources & evidence

ORD record
ord-63a0248215934cbc8c023d58d64e6061
Source dataset
uspto-grants-1998_11
Patent number
US05830881

Reaction notes

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