2,4,6-Trimethylpyridine → (3R,4R)-1-benzyloxycarbonyl-3-methanesulfonyloxy-4-methanesulfonyloxymethylpyrrolidine

HRID 859885Notes

Reaction equation

HRID 859885 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[C@@H:13]([CH2:17][OH:18])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C(C)=CC(C)=CC=1C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][C@H:13]([CH2:17][O:18][S:29]([CH3:28])(=[O:31])=[O:30])[C@@H:14]([O:16][S:29]([CH3:28])(=[O:31])=[O:30])[CH2:15]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:1]([O:8][C:9]([N:11]1[CH2:12][C@H:13]([CH2:17][O:18][S:29]([CH3:28])(=[O:31])=[O:30])[C@@H:14]([OH:16])[CH2:15]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 79532,4,6-TrimethylpyridineHCID 31297Methanesulfonyl chlorideHCID 66704861(3R,4R)-(1-benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl)methanol

Product 2

HCID 86600234(3R,4R)-1-benzyloxycarbonyl-3-methanesulfonyloxy-4-methanesulfonyloxymethylpyrrolidineHCID 86600235(3R,4R)-1-benzyloxycarbonyl-3-hydroxy-4-methanesulfonyloxymethylpyrrolidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Process (C): (3R,4R)-[1-Benzyloxycarbonyl-4-hydroxypyrrolidin-3-yl]methanol (150 mg) was dissolved in dichloromethane (12 mL) and 2,4,6-collidine (0.79 mL) was added. While this solution was cooled on an ice bath, methanesulfonyl chloride (46.2 μL) was added dropwise. The mixture was then stirred for 2 hours on the ice bath and was allowed to stand for 15 hours in a refrigerator (3° C.). Subsequently, the reaction mixture was sequentially washed with water (2 mL), 1 mol/L hydrochloric acid (2×2 mL), and a saturated aqueous solution of sodium chloride (2×2 mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=1:2 shifted to ethyl acetate) to give 38.7 mg of (3R,4R)-1-benzyloxycarbonyl-3-methanesulfonyloxy-4-methanesulfonyloxymethylpyrrolidine as a pale yellow syrup-like product and 133 mg of (3R,4R)-1-benzyloxycarbonyl-3-hydroxy-4-methanesulfonyloxymethylpyrrolidine as a white syrup-like product.

Workup

  1. temperatureWhile this solution was cooled on an ice bath
  2. washSubsequently, the reaction mixture was sequentially washed with water (2 mL), 1 mol/L hydrochloric acid (2×2 mL)
  3. dry with materialby drying over anhydrous sodium sulfate and concentration under reduced pressure
  4. customThe resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=1:2 shifted to ethyl acetate)

Sources & evidence

ORD record
ord-bffea00075ab44409e80c4677e3bf4ef
Source dataset
uspto-grants-2006_12
Patent number
US07153851B2

Reaction notes

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