Hydrochloric Acid → (1s,3r,4s,7r)-7-Benzyloxy-3-(6-n-benzoyladenin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane

HRID 660003Notes

Reaction equation

HRID 660003 reaction equation
[C:1]([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[NH:12][CH:13]=[N:14]2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-:20].Cl.[CH3:22][CH2:23][O:24][C:25]([CH3:27])=O.[CH2:28]1[CH2:32][O:31][CH2:30]C1>[Na+].[Cl-].C(Cl)Cl.[Cl-].[Na+].O>[CH2:23]([O:24][C@H:25]1[C@@H:27]2[O:20][CH2:28][C@@H:32]1[O:31][C@H:30]2[N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][CH:17]=[N:18][C:10]=2[NH:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:22]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 970756-Benzamidopurine2×

Product 1

HCID 68487695(1s,3r,4s,7r)-7-Benzyloxy-3-(6-n-benzoyladenin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane

Reagents, catalysts & solvents 3

HCID 5234Sodium ChlorideSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Pure 62 (100 mg, 0.128 mmol) was dissolved in THF (7 ml), cooled to 0° C. and added 1 M LiOH (1.3 ml, 10 equiv.). The reaction mixture was allowed to slowly reach r.t. When LCMS confirmed full conversion of 62 to 63, the reaction was neutralized with 1 M HCl satd. with NaCl (1.3 ml), diluted with DCM (20 ml) and brine (10 ml). Layers were separated and the aqueous layer was extracted with DCM (2×20 ml). Comb. organic layers were dried (Na2SO4), filtered and the solvent removed in vacuo to afford a clear oil (63)2 (quantitative yield). Rf=0.49 (Eluent: EtOAc). ESI-MS m/z found 552.2 ([MH]+, calcd 552.1); 1H-NMR (CDCl3, 400 MHz): 8.64 (1H, s, N—H), 8.44 (1H, s, Adenin), 7.95 (2H, d, J=7.1 Hz, Bz), 7.50 (1H, t, J=7.3 Hz, Bz), 7.40 (1H, t, J=7.3 Hz, Bz), 7.07-6.79 (5H, m, OBn), 6.11 (1H, s, H-1′), 4.66 (1H, d, J=11.5 Hz, CH2), 4.61 (1H, d, J=11.5 Hz, CH2), 4.48 (1H, d, J=1.8 Hz, H-2′/H-3′), 4.30 (1H, d, J=11.9 Hz, CH2), 4.12 (1H, d, J=11.9 Hz, CH2), 4.07 (1H, d, J=1.8 Hz, H-3′/H-2′) 4.02 (1H, d, J=8.6 Hz, CH2), 3.94 (1H, d, J=8.6 Hz, CH2), 3.02 (3H, s, OMs); 13C-NMR (CDCl3, 100 MHz): δ 165.31, 152.03, 150.45, 148.54, 141.99, 135.38, 132.90, 132.84, 128.63, 128.37, 128.26, 127.98, 127.88, 121.34, 87.90, 86.16, 79.84, 76.29, 73.45, 72.51, 67.76, 64.47, 37.48 (OMs). 2Compound 63 is also described in JACS 124, p. 2164-2176 (2002) but not as an isolated product.

Workup

  1. customwas allowed to slowly reach r.t
  2. customLayers were separated
  3. extractionthe aqueous layer was extracted with DCM (2×20 ml)
  4. dry with materialorganic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customto afford a clear oil (63)2 (quantitative yield)

Sources & evidence

ORD record
ord-673f831711484b56973ee70ed03aa2fd
Source dataset
uspto-grants-2011_12
Patent number
US08084458B2

Reaction notes

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