Chloride → HCID 52914724, compound

HRID 1944091Notes

Reaction equation

HRID 1944091 reaction equation
[Cl-].CS(C)=O.[CH2:6]([O:13][C@H:14]1[C@H:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@@H:18]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@H:17]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([CH2:43][C:44]3[CH:49]=[CH:48][C:47]([O:50][CH2:51][CH3:52])=[CH:46][CH:45]=3)[CH:37]=2)[O:16][C@@H:15]1[CH2:53][OH:54])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C.[OH-:62].[Na+].[CH2:64]=O>C(Cl)Cl.O.C1OCCOC1>[CH2:6]([O:13][C@H:14]1[C@H:19]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@@H:18]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@H:17]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([CH2:43][C:44]3[CH:45]=[CH:46][C:47]([O:50][CH2:51][CH3:52])=[CH:48][CH:49]=3)[CH:37]=2)[O:16][C:15]1([CH2:64][OH:62])[CH2:53][OH:54])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

10

Reactant 6

HCID 312ChlorideHCID 679Dimethyl SulfoxideHCID 712FormaldehydeHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 67074671HCID 67074671, compound

Product 1

HCID 52914724HCID 52914724, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent3×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of oxallyl chloride (0.05 mL, 0.718 mmole) in dry DCM (5 mL), DMSO (0.1 mL, 1.43 mmole) in DCM (1 mL) was added at −70° C. and stirred for 10 min., Solution of {(2R,3R,4R,5S,6S)-3,4,5-tris-benzyloxy-6-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-tetrahydro-pyran-2-yl}-methanol (500 mg, 0.718 mmole) in DCM (4 mL) was added during 15 min at −70° C. and reaction mixture stirred for 1 hour. Triethylamine (0.5 mL, 3.5 mmole) was added and allowed stir at room temperature for 15 min. The reaction mixture was diluted with water (25 mL) and the organic layer washed with 1N HCl (10 mL), saturated aqueous NaHCO3 (10 mL), extracted with DCM (2×25 mL). The crude product obtained after the removal of solvent was co evaporated with toluene (20×4) to furnish crude aldehyde. To this crude aldehyde, 1-4 dioxane (10 mL), 1N NaOH (2 mL), 37% aq. formaldehyde (2 mL) were added and stirred for 72 hours at room temperature. The reaction mixture was diluted with water (25 mL) and washed with 1N HCl (15 mL), extracted with ethyl acetate (2×25 mL). The crude product obtained after the removal of solvent was purified using silica gel column chromatography (20% ethyl acetate in hexane) to furnish 210 mg of {(3S,4R,5S,6S)-3,4,5-tris-benzyloxy-6-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-2-hydroxymethyl-tetrahydro-pyran-2-yl}-methanol.

Workup

  1. customreaction mixture
  2. stirringstirred for 1 hour
  3. stirringallowed stir at room temperature for 15 min
  4. washthe organic layer washed with 1N HCl (10 mL), saturated aqueous NaHCO3 (10 mL)
  5. extractionextracted with DCM (2×25 mL)
  6. customThe crude product obtained
  7. customafter the removal of solvent
  8. customwas co evaporated with toluene (20×4)
  9. customto furnish crude aldehyde
  10. stirringstirred for 72 hours at room temperature
  11. washwashed with 1N HCl (15 mL)
  12. extractionextracted with ethyl acetate (2×25 mL)
  13. customThe crude product obtained
  14. customafter the removal of solvent
  15. customwas purified

Sources & evidence

ORD record
ord-9b1cd7172c2d4d59a46659f3d6215087
Source dataset
uspto-grants-2013_03
Patent number
US08394772B2

Reaction notes

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