Hydrochloric Acid → (2R,4R)-1-allyloxycarbonyl-2-[2-(4-hydroxymethylimidazol-1-yl) ethyl]-4-methanesulfonyloxypyrrolidine

HRID 975706Notes

Reaction equation

HRID 975706 reaction equation
[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([O:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH2:9][C@H:8]1[CH2:17][CH2:18][N:19]1[CH:23]=[C:22]([CH2:24][O:25][Si](C(C)(C)C)(C)C)[N:21]=[CH:20]1)=[O:6])[CH:2]=[CH2:3].Cl>C(#N)C>[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([O:12][S:13]([CH3:16])(=[O:14])=[O:15])[CH2:9][C@H:8]1[CH2:17][CH2:18][N:19]1[CH:23]=[C:22]([CH2:24][OH:25])[N:21]=[CH:20]1)=[O:6])[CH:2]=[CH2:3]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 54108174(2R,4R)-1-allyloxycarbonyl-2-[2-{4-(t-butyldimethylsilyloxymethyl)-imidazol-1-yl}ethyl]-4-methanesulfonyloxypyrrolidine

Product 1

HCID 54192133(2R,4R)-1-allyloxycarbonyl-2-[2-(4-hydroxymethylimidazol-1-yl) ethyl]-4-methanesulfonyloxypyrrolidineYield 33.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (2R,4R)-1-allyloxycarbonyl-2-[2-{4-(t-butyldimethylsilyloxymethyl)imidazol-1-yl}ethyl]-4-methanesulfonyloxypyrrolidine (23.7 g) in acetonitrile (120 ml) was added concentrated hydrochloric acid (12 ml) dropwise under cooling in an ice-bath. After stirring at the same temperature for 2 hours, the mixture was quenched by the addition of a solution of sodium methoxide in methanol (28% W/W, 27.8 g) then ethyl acetate (240 ml) was added. The precipitate was filtered off and the filtrate was concentrated in vacuo. The residue was dissolved in acetonitrile (120 ml) and dried over magnesium sulfate. The solution was filtered and the filtrate was washed with hexane (200 ml×5) then concentrated in vacuo. The residual yellow paste was chromatographed on a 140 g of silica gel eluting with a mixture of chloroform and methanol (100:0 to 99:1 to 95:5) to give (2R,4R)-1-allyloxycarbonyl-2-[2-(4-hydroxymethylimidazol-1-yl) ethyl]-4-methanesulfonyloxypyrrolidine (6.02 g) as a yellow paste.

Workup

  1. temperatureunder cooling in an ice-bath
  2. customthe mixture was quenched by the addition of a solution of sodium methoxide in methanol (28% W/W, 27.8 g)
  3. additionethyl acetate (240 ml) was added
  4. filtrationThe precipitate was filtered off
  5. concentrationthe filtrate was concentrated in vacuo
  6. dissolutionThe residue was dissolved in acetonitrile (120 ml)
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe solution was filtered
  9. washthe filtrate was washed with hexane (200 ml×5)
  10. concentrationthen concentrated in vacuo
  11. customThe residual yellow paste was chromatographed on a 140 g of silica gel eluting with a mixture of chloroform and methanol (100:0 to 99:1 to 95:5)

Sources & evidence

ORD record
ord-bed39e3f22b14680a4e18508cd191a06
Source dataset
uspto-grants-1997_03
Patent number
US05608056

Reaction notes

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