Acetic Acid → HCID 69543941, compound

HRID 891722Notes

Reaction equation

HRID 891722 reaction equation
[Si]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28](=[O:48])[NH:29][C@H:30]3[CH2:34][CH2:33][N:32]([C:35]([O:37][CH2:38][C:39]4[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][CH:40]=4)=[O:36])[CH2:31]3)[N:27]=2)[CH2:20]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>O1CCCC1.O>[OH:18][CH:19]1[CH2:20][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28](=[O:48])[NH:29][C@H:30]3[CH2:34][CH2:33][N:32]([C:35]([O:37][CH2:38][C:39]4[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][CH:40]=4)=[O:36])[CH2:31]3)[N:27]=2)[CH2:22]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 69544039HCID 69544039, compound

Product 1

HCID 69543941HCID 69543941, compoundYield 98.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-t-butyldiphenylsilyloxy-1-{4-[(3S)-1-(p-nitrobenzyloxycarbonyl)-pyrrolidin-3-ylcarbamoyl]-1,3-thiazol-2-yl}azetidine (560 mg, 0.816 mmol) (obtained as described in Reference Example 52(5)) in anhydrous tetrahydrofuran (17 ml) was added successively acetic acid (56 μl, 0.980 mmol) and a solution of 1.0M tetra-n-butylammonium fluoride in tetrahydrofuran (980 μl, 0.980 mmol) in an ice bath. The mixture was stirred in the ice bath for 1.5 hours. After checking the completion of the reaction, ethyl acetate and water were added thereto and the aqueous layer was extracted with ethyl acetate. The obtained organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using ethyl acetate→ethyl acetate:methanol (95:1) as the eluant to afford 3-hydroxy-1-{4-[(3S)-1-(p-nitrobenzyloxycarbonyl)-pyrrolidin-3-ylcarbamoyl]-1,3-thiazol-2-yl}azetidine (359 mg, yield 98%) as a white solid.

Workup

  1. additionwere added
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washThe obtained organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-036af7dff53e4a94aff9717bc0a36af2
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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