Acetic Acid → HCID 67150767, compound

HRID 2353041Notes

Reaction equation

HRID 2353041 reaction equation
C[O:2][C:3](=[O:37])[CH2:4][CH2:5][CH:6]1[CH:13]2[CH:9]([O:10][CH:11]([CH:14]=[CH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12]2)[CH:8]([N:22]2[CH:30]=[N:29][C:28]3[C:23]2=[N:24][CH:25]=[N:26][C:27]=3[NH:31][C:32]([NH:34][CH2:35][CH3:36])=[O:33])[O:7]1.O.[OH-].[Li+].C(O)(=O)C>O1CCCC1>[CH2:35]([NH:34][C:32](=[O:33])[NH:31][C:27]1[N:26]=[CH:25][N:24]=[C:23]2[C:28]=1[N:29]=[CH:30][N:22]2[CH:8]1[CH:9]2[O:10][CH:11]([CH:14]=[CH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12][CH:13]2[CH:6]([CH2:5][CH2:4][C:3]([OH:37])=[O:2])[O:7]1)[CH3:36]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 67150706HCID 67150706, compound

Product 1

HCID 67150767HCID 67150767, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-{6-[6-(3-Ethyl-ureido)-purin-9-yl]-2-styryl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl}-propionic acid methyl ester (5.0 g, 10 mmol) was dissolved in tetrahydrofuran (300 mL). Water (100 mL) was added, followed by lithium hydroxide (1.0 g, 25 mmol). The solution was allowed to stir 16 h at room temperature. It was acidified to pH 5 with acetic acid, concentrated in vacuo, then extracted with chloroform (300 mL). The organic extract was evaporated, redissolved in ethyl acetate and precipitated with heptane to afford the title compound (3.9 g, 80%), as a mixture of acetal diastereomers. Compound 183, which is the trans diastereomer contained within the acetal mixture, was obtained by separation on a chiral HPLC column. (Phenomenex Synergi Polar RP chiral C18 column). Alternately, Compound 183 was obtained by subjecting the diastereomeric mixture of acetals to aqueous acid conditions (for example 65% aqueous acetic acid at 50° C. or aqueous p-toluenesulfonic acid at 30° C.), which cleaved the less stable cis diastereomer, leaving the trans isomer (Compound 183) intact. 1H-NMR of the diastereomeric mixture of acetals(300 MHz, d6DMSO) δ 1.14 (t 3H, J=7 Hz), 1.90 (m, 2H), 2.19 (m, 2H), 3.26 (q, 2H, J=6 Hz), 4.17 (m, 1H), 4.93 (ψt, 1H, J=6 Hz), 5.43 (dd, 1H, J=3 Hz, 7 Hz), 5.84 (d 1H, J=6 Hz), 6.24 (d, 1H, J=3 Hz), 6.28 (dd, 1H, J=7 Hz, 13 Hz), 6.90 (d, 1H, J 16 Hz), 7.35 (m, 3H), 7.51 (d, 2H, J=7 Hz), 8.56 (s, 1H), 8.61 (s, 1H), 9.30 (t, 1H, J=6 Hz).

Workup

  1. concentrationconcentrated in vacuo
  2. extractionextracted with chloroform (300 mL)
  3. extractionThe organic extract
  4. customwas evaporated
  5. dissolutionredissolved in ethyl acetate
  6. customprecipitated with heptane

Sources & evidence

ORD record
ord-086ee26b69e647348e56c861a2a0628b
Source dataset
uspto-grants-2010_07
Patent number
US07749981B2

Reaction notes

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