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

HRID 891509Notes

Reaction equation

HRID 891509 reaction equation
[C:1]([CH2:4][N:5]([CH3:50])[C:6]([C:8]1[N:9]=[C:10]([N:13]2[CH2:16][CH:15]([S:17][C:18]3[C@H:19]([CH3:49])[C@@H:20]4[C@@H:37]([C@H:38]([O:40][Si](C(C)(C)C)(C)C)[CH3:39])[C:36](=[O:48])[N:21]4[C:22]=3[C:23]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=3)=[O:24])[CH2:14]2)[S:11][CH:12]=1)=[O:7])(=[O:3])[NH2:2].C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[C:1]([CH2:4][N:5]([CH3:50])[C:6]([C:8]1[N:9]=[C:10]([N:13]2[CH2:16][CH:15]([S:17][C:18]3[C@H:19]([CH3:49])[C@@H:20]4[C@@H:37]([C@H:38]([OH:40])[CH3:39])[C:36](=[O:48])[N:21]4[C:22]=3[C:23]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=3)=[O:24])[CH2:14]2)[S:11][CH:12]=1)=[O:7])(=[O:3])[NH2:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 131725328p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[N-methyl-N-(carbamoyl)methyl-carbamoyl]-1,3-thiazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725327p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(carbamoylmethyl-methyl-carbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylateYield 53%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(carbamoylmethyl-methyl-carbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl)thio-6-[(R)-1-t-butyidimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (932 mg, 1.27 mmol) (obtained as described in Reference Example 44(2)) in tetrahydrofuran (50 ml) were added acetic acid (0.22 ml, 3.81 mmol) and 1 M tetrabutylammonium fluoride in tetrahydrofuran solution (3.81 ml, 3.81 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 saturated aqueous sodium hydrogencarbonate 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 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 (10:1)) to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(carbamoylmethyl-methyl-carbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (424 mg, yield 53%) 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 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 (10:1))

Sources & evidence

ORD record
ord-4d6e8b9e5bb4410898ec70ed3cb55ad5
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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