Hydrochloric Acid → (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl) (isobutyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propylcarbamate

HRID 1815591Notes

Reaction equation

HRID 1815591 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([S:10]([N:13]([CH2:18][C@H:19]3[O:23]C(C)(C)[N:21]([C:26]([O:28][C@@H:29]4[C@H:36]5[C@H:32]([O:33][CH2:34][CH2:35]5)[O:31][CH2:30]4)=[O:27])[C@H:20]3[CH2:37][C:38]3[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=3)[CH2:14][CH:15]([CH3:17])[CH3:16])(=[O:12])=[O:11])=[CH:9][C:4]=2[O:3][CH2:2]1.Cl.[OH-].[Na+]>O1CCOCC1.C(Cl)Cl.O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([S:10]([N:13]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:18][C@@H:19]([OH:23])[C@@H:20]([NH:21][C:26](=[O:27])[O:28][C@@H:29]3[C@H:36]4[C@H:32]([O:33][CH2:34][CH2:35]4)[O:31][CH2:30]3)[CH2:37][C:38]3[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=3)(=[O:12])=[O:11])=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 45358743HCID 45358743, compound

Product 1

HCID 59997191(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl) (isobutyl)amino]-2-hydroxy-1-(4-hydroxybenzyl)propylcarbamateYield 81%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 0.60 g (0.95 mmol) of (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (4S,5R)-5-{[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]methyl}-4-(4-hydroxybenzyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate in 5 mL of 1,4-dioxane was treated with 0.25 mL of water followed by 5 mL of 4N HCl in 1,4-dioxane and the resulting solution was stirred at RT. After 1.5 hours the solution was diluted with 25 mL of CH2Cl2 and the pH adjusted to approximately 12 by addition of 1N aqueous NaOH. The mixture was diluted with water and extracted with CH2Cl2 (3×). The combined CH2Cl2 extracts were washed with aqueous brine (3×), dried over MgSO4, and concentrated in vacuo. The residue was subjected to flash chromatography (SiO2, 8:2 EtOAc/hexane) to afford the desired compound as a white solid in 81% yield. 1H NMR (CDCl3): 7.29 (dd, 1H), 7.13 (s, 1H), 7.01 (d, 2H), 6.85 (d, 2H), 6.70 (d, 2H), 6.05 (s, 2H), 5.61 (d, 1H), 5.01 (m, 2H), 3.92 (dd, 1H), 3.80 (m, 4H), 3.68 (m, 2H), 3.08 (dd, 1H), 2.91 (m, 5H), 2.81-2.62 (m, 2H), 1.80 (m, 1H), 1.64 (m, 1H), 1.47 (m, 1H), 0.90 (d, 3H), 0.82 (d, 3H). MS(ESI): 593(M+H).

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. washThe combined CH2Cl2 extracts were washed with aqueous brine (3×)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bf73898f4b9b4416a957aed0c346f42b
Source dataset
uspto-grants-2005_04
Patent number
US06878728B1

Reaction notes

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