Chloride → HCID 52914724, compound

HRID 1944087Notes

Reaction equation

HRID 1944087 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.Cl>C(Cl)Cl.O>[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 7

HCID 312ChlorideHCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 712FormaldehydeHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 67074671HCID 67074671, compound

Product 1

HCID 52914724HCID 52914724, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of oxallyl chloride (0.05 mL, 0.72 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, 0.72 mmole) in DCM (4 mL) was added during 15 min at −70° C. and the reaction mixture stirred for 1 hour. Triethylamine (0.5 mL, 3.5 mmole) was added and allowed to stir at room temperature for 15 min. The reaction mixture was diluted with water (25 mL) and extracted with DCM (2×25 mL). The combined organic layer washed with 1N HCl (10 mL), saturated aqueous NaHCO3 (10 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. HCHO (2 mL) were added and stirred for 72 hours at room temperature. The reaction mixture was diluted with water (25 mL) and neutralized with 1N HCl, 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. stirringthe reaction mixture stirred for 1 hour
  2. stirringto stir at room temperature for 15 min
  3. extractionextracted with DCM (2×25 mL)
  4. washThe combined organic layer washed with 1N HCl (10 mL), saturated aqueous NaHCO3 (10 mL)
  5. customThe crude product obtained
  6. customafter the removal of solvent
  7. customwas co evaporated with toluene (20×4)
  8. customto furnish crude aldehyde
  9. stirringstirred for 72 hours at room temperature
  10. extractionextracted with ethyl acetate (2×25 mL)
  11. customThe crude product obtained
  12. customafter the removal of solvent
  13. customwas purified

Sources & evidence

ORD record
ord-0583b797459e4eedb67acd68d3fac6bd
Source dataset
uspto-grants-2013_03
Patent number
US08394772B2

Reaction notes

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