Hydrochloric Acid → (3R,5S)-allyloxycarbonyl-5-(5-chloroimidazo[5,1-b]thiazol-2-yl)methyl-3-hydroxypyrrolidine

HRID 568296Notes

Reaction equation

HRID 568296 reaction equation
[CH2:1]([O:4][C:5]([N:7]1[C@H:11]([CH2:12][C:13]2[S:17][C:16]3=[CH:18][N:19]=[C:20]([Cl:21])[N:15]3[CH:14]=2)[CH2:10][C@@H:9]([O:22][Si](C(C)(C)C)(C)C)[CH2:8]1)=[O:6])[CH:2]=[CH2:3].Cl>C(#N)C.C(OCC)(=O)C>[CH2:1]([O:4][C:5]([N:7]1[C@H:11]([CH2:12][C:13]2[S:17][C:16]3=[CH:18][N:19]=[C:20]([Cl:21])[N:15]3[CH:14]=2)[CH2:10][C@@H:9]([OH:22])[CH2:8]1)=[O:6])[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 20639583(3R,5s)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-(5-chloroimidazo[5,1-b]thiazol-2-yl)methylpyrrolidine

Product 1

HCID 20639586(3R,5S)-allyloxycarbonyl-5-(5-chloroimidazo[5,1-b]thiazol-2-yl)methyl-3-hydroxypyrrolidineYield 95.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.430 g of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-(5-chloroimidazo[5,1-b]thiazol-2-yl)methylpyrrolidine in 31.5 ml of dry acetonitrile is cooled to 3° C., 1.3 ml of concentrated hydrochloric acid is added dropwise thereto while maintaining the internal temperature at 4° C. or below, and the mixture is stirred in this state for 15 min. The reaction solution is diluted with 200 ml of ethyl acetate, washed with 40 ml of a 5% aqueous sodium hydrogencarbonate solution (aqueous layer pH 9) and dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure to give a crude product which is then purified by column chromatography on silica gel (ethyl acetate) to give 1.020 g of (3R,5S)-allyloxycarbonyl-5-(5-chloroimidazo[5,1-b]thiazol-2-yl)methyl-3-hydroxypyrrolidine as a slightly yellow viscous material.

Workup

  1. temperaturewhile maintaining the internal temperature at 4° C. or below
  2. washwashed with 40 ml of a 5% aqueous sodium hydrogencarbonate solution (aqueous layer pH 9)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent is removed by evaporation under reduced pressure
  5. customto give a crude product which
  6. customis then purified by column chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-740a21f2de0c46dba004337e8e0328e3
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

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