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

HRID 891508Notes

Reaction equation

HRID 891508 reaction equation
[N+:1]([C:4]1[CH:59]=[CH:58][C:7]([CH2:8][O:9][C:10]([CH2:12][NH:13][C:14]([C:16]2[N:17]=[C:18]([N:21]3[CH2:24][CH:23]([S:25][C:26]4[C@H:27]([CH3:57])[C@@H:28]5[C@@H:45]([C@H:46]([O:48][Si](C(C)(C)C)(C)C)[CH3:47])[C:44](=[O:56])[N:29]5[C:30]=4[C:31]([O:33][CH2:34][C:35]4[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=4)=[O:32])[CH2:22]3)[S:19][CH:20]=2)=[O:15])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[N+:1]([C:4]1[CH:59]=[CH:58][C:7]([CH2:8][O:9][C:10]([CH2:12][NH:13][C:14]([C:16]2[N:17]=[C:18]([N:21]3[CH2:24][CH:23]([S:25][C:26]4[C@H:27]([CH3:57])[C@@H:28]5[C@@H:45]([C@H:46]([OH:48])[CH3:47])[C:44](=[O:56])[N:29]5[C:30]=4[C:31]([O:33][CH2:34][C:35]4[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=4)=[O:32])[CH2:22]3)[S:19][CH:20]=2)=[O:15])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 131725326p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(p-nitrobenzyloxycarbonylmethyl)carbamoyl-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate

Product 1

HCID 131725325p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(p-nitrobenzyloxycarbonylmethyl-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-(p-nitrobenzyloxycarbonylmethyl-carbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-t-butyldimethylsilyloxyethyl]-1-methylcarbapen-2-em-3-carboxylate (209.7 mg, 0.24 mmol) (obtained as described in Reference Example 41(10)) in tetrahydrofuran (10 ml) was added acetic acid (0.042 ml, 0.7 mmol) and 1 M tetrabutylammonium fluoride in tetrahydrofuran solution (0.72 ml, 0.72 mmol) in an ice bath and the mixture was stirred at room temperature for 4 days. After checking the completion of the reaction, ethyl acetate and saturated aqueous sodium hydrogencarbonate solution 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: toluene: acetonitrile (2:1)) to afford p-nitrobenzyl (1R,5S,6S)-2-{1-[4-(p-nitrobenzyloxycarbonylmethyl-carbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl}thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (94.5 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: toluene: acetonitrile (2:1))

Sources & evidence

ORD record
ord-91bc274e004c4d4580e5b9eb7ed66f6b
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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