Acetic Acid → p-nitrobenzyl (1R,5S,6S)-2-{1-[4-((1S)-1-carbamoyl-2-methyl-propylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

HRID 891511Notes

Reaction equation

HRID 891511 reaction equation
[C:1]([C@@H:4]([NH:8][C:9]([C:11]1[N:12]=[C:13]([N:16]2[CH2:19][CH:18]([S:20][C:21]3[C@H:22]([CH3:52])[C@@H:23]4[C@@H:40]([C@H:41]([O:43][Si](C(C)(C)C)(C)C)[CH3:42])[C:39](=[O:51])[N:24]4[C:25]=3[C:26]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][CH:31]=3)=[O:27])[CH2:17]2)[S:14][CH:15]=1)=[O:10])[CH:5]([CH3:7])[CH3:6])(=[O:3])[NH2:2].C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>O1CCCC1.O>[C:1]([C@@H:4]([NH:8][C:9]([C:11]1[N:12]=[C:13]([N:16]2[CH2:17][CH:18]([S:20][C:21]3[C@H:22]([CH3:52])[C@@H:23]4[C@@H:40]([C@H:41]([OH:43])[CH3:42])[C:39](=[O:51])[N:24]4[C:25]=3[C:26]([O:28][CH2:29][C:30]3[CH:31]=[CH:32][C:33]([N+:36]([O-:38])=[O:37])=[CH:34][CH:35]=3)=[O:27])[CH2:19]2)[S:14][CH:15]=1)=[O:10])[CH:5]([CH3:6])[CH3:7])(=[O:3])[NH2:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 131725332p-nitrobenzyl (1R,5S,6S)-2-{1-[4-((1S)-1-carbamoyl-2-methyl-propylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725331p-nitrobenzyl (1R,5S,6S)-2-{1-[4-((1S)-1-carbamoyl-2-methyl-propylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylateYield 48.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of p-nitrobenzyl (1R,5S,6S)-2-{1-[4-((1S)-1-carbamoyl-2-methyl-propylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (930 mg, 1.20 mmol) (obtained as described in Reference Example 47(3)) in tetrahydrofuran (47 ml) was added acetic acid (206 μl, 3.60 mmol) and 1 M tetrabutylammonium fluoride in tetrahydrofuran solution (3.60 ml, 3.60 mmol) in an ice bath and the mixture was stirred at room temperature for 2 days. After checking the completion of the reaction, ethyl acetate and water were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the ethyl acetate layer was separated, washed with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluant: ethyl acetate→ethyl acetate: methanol (95:5)) to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-((1S)-1-carbamoyl-2-methyl-propylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (383 mg, yield 48%) as a pale yellow solid.

Workup

  1. additionwere added to the reaction mixture
  2. stirringThe resulting mixture was shaken in a separatory funnel
  3. customthe ethyl acetate layer was separated
  4. washwashed with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on a silica gel column (eluant: ethyl acetate→ethyl acetate: methanol (95:5))

Sources & evidence

ORD record
ord-1ebca53a1d7d4538b05ea58305be13a6
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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