Ammonium Chloride → (3R,5S)-1-Allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidine

HRID 568279Notes

Reaction equation

HRID 568279 reaction equation
C[Mg]I.C(OCC)C.I[C:10]1[N:11]=[CH:12][N:13]2[CH:17]=[CH:16][S:15][C:14]=12.[CH2:18]([O:21][C:22]([N:24]1[C@H:28]([CH:29]=[O:30])[CH2:27][C@@H:26]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:25]1)=[O:23])[CH:19]=[CH2:20].[Cl-].[NH4+]>C1COCC1>[CH2:18]([O:21][C:22]([N:24]1[C@H:28]([CH:29]([OH:30])[C:10]2[N:11]=[CH:12][N:13]3[CH:17]=[CH:16][S:15][C:14]=23)[CH2:27][C@@H:26]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[CH3:34])[CH2:25]1)=[O:23])[CH:19]=[CH2:20]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 177737777-Iodoimidazo[5,1-B]thiazoleHCID 22870383(2S,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-formylpyrrolidineHCID 178467823HCID 178467823, compound

Product 1

HCID 20639579(3R,5S)-1-Allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-50 °C

Procedure

A 2 M methylmagnesium iodide/diethyl ether solution (4.6 ml) is diluted with 50 ml of anhydrous THF, and a solution of 2.0 g of 7-iodoimidazo[5,1-b]thiazole in 50 ml of THF is added dropwise to the diluted solution under ice cooling in an argon atmosphere. The mixture is stirred at that temperature for 10 min and then at room temperature for 1.5 hr and cooled to −50° C., and a solution of 1.735 g of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-formylpyrrolidine in 50 ml of THF is added dropwise thereto. A reaction is allowed to proceed while raising the temperature to 10° C. over a period of 3 hr, 200 ml of a semi-saturated aqueous ammonium chloride solution is added thereto, and the mixture is extracted twice with 250 ml of ethyl acetate. The organic layer is dried over anhydrous magnesium sulfate and filtered, and the solvent is removed by evaporation. The residue is purified by column chromatography on silica gel (ethyl acetate alone→ethyl acetate:methanol=20:1→10:1). Thus, 450 mg of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidine (stereoisomer A: a high polar component) and 395 mg of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[l-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidine (stereoisomer B: a low polar component) are prepared.

Workup

  1. waitat room temperature for 1.5 hr
  2. temperaturewhile raising the temperature to 10° C. over a period of 3 hr
  3. extractionthe mixture is extracted twice with 250 ml of ethyl acetate
  4. dry with materialThe organic layer is dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent is removed by evaporation
  7. customThe residue is purified by column chromatography on silica gel (ethyl acetate alone→ethyl acetate
  8. customThus, 450 mg of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidine (stereoisomer A: a high polar component) and 395 mg of (3R,5S)-1-allyloxycarbonyl-3-t-butyldimethylsilyloxy-5-[l-hydroxy-1-(imidazo[5,1-b]thiazol-7-yl)methyl]pyrrolidine (stereoisomer B: a low polar component) are prepared

Sources & evidence

ORD record
ord-d74296933a934beb9827fcb70742da83
Source dataset
uspto-grants-2001_01
Patent number
US06180622B2

Reaction notes

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